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The bilateral US-Thailand relationship may soon play a major role in protecting the population of Southeast Asia from COVID-19. Negotiations have been underway since October between American vaccine maker INOVIO Pharmaceuticals, Inc., and several Thai parties, including National Vaccine Institute (NVI ) and Innobic (Asia) Company Limited along with other investors.
The intent is to establish vaccine trials, manufacturing, and cooperation in medical research and development that will benefit the region’s population of two billion people. With its innovative DNA-based medicine platform, INOVIO may also establish a medical science role within Thailand’s Eastern Economic Corridor.
While details are still being discussed, plans include Phase 3 trials of INOVIO’s COVID-19 vaccine in India, booster trials in Thailand, and scaled vaccine manufacturing in the region. INOVIO’s vaccine, which is entirely organic with no synthetic ingredients, is injected in the skin and then introduced through the cellular wall using an electroporation delivery device.
This method is designed to generate immunity to COVID-19 combining antibodies as well as a strong T-cell response. INOVIO medicines have been in development for 20 years, and Phase 1 and 2 trials have recorded an excellent safety profile, without severe side effects.
INOVIO’s vaccine was the only DNA-based COVID-19 vaccine selected by the World Health Organization to participate in its international “Solidarity” Phase 3 trial. The company has also obtained approval for Phase 3 trials in the Philippines, Mexico, Colombia, and Brazil.
Unlike other types of COVID-19 vaccines that must be maintained at very cold temperatures, INOVIO’s vaccine remains potent for a year at room temperature without refrigeration. This can save logistical expenses and enable more people to be vaccinated at a lower cost.
While it prepares to play a significant role in meeting the vaccination needs of the global population, INOVIO has enlisted as strategic advisor, General Gus Perna, the retired US Army General who ran Operation Warp Speed in 2020 in the United States.
General Perna previously served as Commander of the US Army Materiel Command, and before that was the Assistant Chief of Staff for Logistics.
https://www.bangkokpost.com/thailand/pr/2231751/anthony-blinken-visits-thailand-to-discuss-thailand-as-a-regional-centre-of-health-protection
2/24/22 Benzinga: Thinking About Buying Stock In AMC Entertainment, Romeo Power Or Inovio Pharmaceuticals?
The latest price target for Inovio was by B of A Securities on Jan. 21. The analyst firm set a price target for $10, a possible 236.70% upside. Five analyst firms have reported ratings in the last year.
Inovio’s fourth-quarter earnings report is confirmed for Tuesday’s after-hours session.
Inovio is a biotechnology company that develops active DNA-based immunotherapies and vaccines to treat and prevent cancers and infectious diseases.
https://www.google.com/amp/s/www.benzinga.com/amp/content/25805525
2/23/22 GSK/SNY vaccine is given in two doses delivered about three weeks apart. The phase 3 trials to test the vaccine enrolled more than 10,000 adults in the US, Asia, Africa and Latin America. A separate study is assessing a third dose of the vaccine as a booster.
After two doses given to people with no antibodies against the SARS-CoV-2 virus, the vaccine was:
58% effective at preventing Covid-19 symptoms
75% effective at preventing moderate or severe Covid-19
100% effective against severe Covid-19 disease, including hospitalizations
The new vaccine posted lower numbers against symptomatic illness than the mRNA vaccines made by Pfizer and Moderna, but it was also tested under different conditions, when the new variants were circulating.
"We're very pleased with these data," said Thomas Triomphe, an executive vice president at Sanofi. "No other global Phase 3 efficacy study has been undertaken during this period with so many variants of concern, including Omicron, and these efficacy data are similar to recent clinical data from authorized vaccines."
The companies said the vaccine performed well on its own and as a mix-and-match booster, bumping neutralizing antibodies by 18- to 30-fold when given to people who'd gotten Pfizer, Moderna or adenovirus-vector vaccines like the Johnson & Johnson and AstraZeneca shots. The manufacturers say there were no safety issues identified in the trials.
A company spokesperson says that the most likely role for the vaccine in the US and European markets — where so many people have completed their initial vaccine series — will be as a booster.
Millions of doses already released
The top-line study results were posted in company news releases. The manufacturers say full results from the trials will be published this year.
The vaccine was developed using $2.1 billion in funding from Operation Warp Speed, the landmark effort to speed effective vaccines against Covid-19 to the US and the rest of the world. The company says it has produced and released 100 million doses and plans to supply up to 400 million more doses.
Vidprevtyn development was delayed after results from an initial formulation showed that it didn't generate a robust immune response in older adults. The companies reformulated and began testing again. The latest results come from a phase 3 trial started in May 2021 and reflect real-world tests of the shots against several variants, including Delta and Omicron.
AstraZeneca to supply Canada with 100,000 doses of Evusheld, a long-acting antibody combination for the prevention of COVID-19
February 23, 2022, 11:30 am
MISSISSAUGA, ON, Feb. 23, 2022 /CNW/ - AstraZeneca Canada has signed an agreement with the Government of Canada for the supply of 100,000 doses of Evusheld (tixagevimab co-packaged with cilgavimab), its long-acting antibody (LAAB) combination for the prevention (pre-exposure prophylaxis) of COVID-19 in those patient populations who require additional protection.
Doses will be delivered in 2022, should Evusheld (the proposed trade name for AZD7442), receive regulatory approval from Health Canada.
[Evusheld is being cloned by $37.6 million grant from DARPA will leverage AstraZeneca's monoclonal antibody and INOVIO's DNA-encoded monoclonal antibody (dMAb®).
COVID-19 dMAbs offer a cost-effective treatment option, are fast to administer to subjects, and can be quickly manufactured and scaled up compared to traditional recombinant monoclonal antibody-based therapies
- dMAbs do not require cold chain transport/storage, and the overall approach can be applied beyond COVID-19 for any pathogen or disease that can be treated by recombinant monoclonal antibody-based therapies.]
In November 2021, AstraZeneca Canada announced it had initiated a rolling review New Drug Submission with Health Canada for the authorization of Evusheld. If granted, Evusheld would be the first LAAB combination to receive Health Canada authorization for COVID-19 prevention.
"Thousands of Canadians remain at serious risk for COVID-19 because they are unable to mount an adequate response to a vaccine due to an underlying health condition or medication they take that compromises their immune system," said Kiersten Combs, President of AstraZeneca Canada. "We are proud to play a leading role in fighting the COVID-19 pandemic and, with Evusheld, we now have an easily-administered, long-lasting option, which we hope will soon be available to offer protection to immune-compromised populations against COVID-19 in Canada."
Approximately 2% of the global population is considered at increased risk of an inadequate response to a COVID-19 vaccine.1,2 Additionally, more than 40% of those hospitalized with breakthrough COVID-19 infections after vaccination are immune-compromised.3,4 This includes people with blood cancers or other cancers being treated with chemotherapy, and those taking medications after an organ transplant or who are taking immunosuppressive drugs for conditions, including multiple sclerosis and rheumatoid arthritis.5-9 Emerging evidence indicates that protecting vulnerable populations from getting COVID-19 could help prevent viral evolution that is an important factor in the emergence of variants.
In August 2021, AstraZeneca announced high-level results of the primary analysis from the PROVENT pre-exposure prophylaxis trial, which showed Evusheld reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. Importantly, the trial population included people with co-morbidities and who may need additional protection from SARS-CoV-2 infection. Greater than 75% of participants in PROVENT presented with co-morbidities associated with an increased risk of severe disease or a reduced immune response to vaccination. Further data of the ongoing PROVENT trial announced in November 2021 demonstrated the long-term benefits with an 83% reduction in the risk of developing symptomatic COVID-19 compared to placebo at a median of 6 months follow-up.
Multiple independent pseudovirus and authentic 'live' virus studies show that Evusheld retains neutralizing activity against the Omicron variant and all other tested variants of concern to date.
About Evusheld
Evusheld is a combination of two LAABs – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein11 and were optimized by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding. The half-life extension more than triples the durability of its action compared to conventional antibodies;12-15 data from the Phase III PROVENT trial show protection lasting at least six months, with the Phase I trial showing high monoclonal antibody titres for at least nine months.
AstraZeneca to supply the US government with an additional one million doses of EVUSHELDTM long-acting antibody combination for the prevention of COVID-19
PUBLISHED
14 February 2022
Builds on initial US government agreement, now totalling 1.7 million doses
Only antibody therapy authorized in the US for pre-exposure prophylaxis of COVID-19 in people who are immunocompromised
AstraZeneca today announced the US Department of Health and Human Services has finalized its agreement to purchase an additional one million doses of EVUSHELDTM (150mg of tixagevimab co-packaged with 150mg of cilgavimab), a long-acting antibody combination for the pre-exposure prophylaxis (prevention) of COVID-19 in immunocompromised populations.
This agreement includes the 500,000 additional dose purchase announced by the US government on January 12, 2022 and follows the government’s initial agreement for the purchase of 700,000 doses of EVUSHELD which are already being administered at sites around the US, for a total of 1.7 million doses. The US government has indicated that it plans to distribute these additional doses to states and territories at no cost.
Multiple independent live and pseudovirus studies showed that EVUSHELD retains neutralizing activity against the Omicron variant and all tested SARS-CoV-2 variants of concern to date.1-4 By combining two particularly potent antibodies with different and complementary activities against the virus, EVUSHELD was designed to evade potential resistance with the emergence of new SARS-CoV-2 variants.
EVUSHELD received Emergency Use Authorization (EUA) in the US on December 8, 2021 for the pre-exposure prophylaxis (prevention) of COVID-19 in adults and adolescents (aged 12 and older who weigh 40kg or more) with moderate to severe immune compromise due to a medical condition or immunosuppressive medications and who may not mount an adequate immune response to COVID-19 vaccination, as well as those individuals for whom COVID-19 vaccination is not recommended due to a history of severe adverse reaction to a COVID-19 vaccine.
3Q21 10-Q Pg 23 Plumbline Life Sciences, Inc.
The Company owned 597,808 shares of common stock in PLS as of September 30, 2021, representing a 19.7% ownership interest, and one of the Company's directors, Dr. David B. Weiner, acts as a consultant to PLS.
Revenue recognized from PLS consists of milestone, license and patent fees. For the three and nine months ended September 30, 2021, the Company recognized revenue from PLS of $95,000 and $220,000, respectively, and $83,000 and $1.3 million, for the three and nine months ended September 30, 2020, respectively. At September 30, 2021 and December 31, 2020, the Company had an accounts receivable balance of $139,000 and $67,000, respectively, related to PLS.
Pg 28 Department of Defense (DoD)
In June 2020, the Company entered into an Other Transaction Authority for Prototype Agreement (the “OTA Agreement”) with the DoD to fund the Company’s efforts in developing the CELLECTRA® 3PSP device and associated arrays to be used for delivery of INO-4800 against COVID-19. Under the OTA Agreement, the Company intends to develop the CELLECTRA® 3PSP device and arrays for use in the U.S. military population and the U.S. population as a whole, subject to approval of the device by the U.S. Food and Drug Administration (the “FDA”). The OTA Agreement is also expected to support large-scale manufacturing of the CELLECTRA® 3PSP device, as well as large-scale DNA plasmid production for manufacture and supply of a specified number of doses of INO-4800 in support of FDA approval of the device. The total amount of funding being made available to the Company under the OTA Agreement is approximately $54.5 million. The Company has determined that the OTA Agreement should be considered under Subtopic 958-605, Not-for-Profit Entities Revenue Recognition, which is outside the scope of Topic 606, as the government agency granting the Company funds is not receiving reciprocal value for their contributions. The Company will record contra-research development expense on the condensed consolidated statement of operations in the same period that the underlying expenses are incurred.
Additionally, in June 2020, the Company was awarded a fixed-price contract (the “Procurement Contract”) from the DoD for the purchase of the Company’s intradermal CELLECTRA® 2000 device and accessories. The CELLECTRA® 2000 devices will be used to inject INO-4800 in the Company’s planned later-stage clinical trials. The total purchase price under the Procurement Contract is approximately $16.6 million. The Company has determined that the Procurement Contract does not currently fall under the scope of ASC 606 as contingencies remain regarding INO-4800 which does not give the Company the ability to satisfy its obligations under the arrangement.
During the three and nine months ended September 30, 2021, the Company recorded $2.4 million and $23.6 million, respectively, as contra-research and development expense related to the OTA Agreement. During the three and nine months ended September 30, 2020, the Company recorded $7.7 million as contra-research and development expense related to the OTA Agreement. As of September 30, 2021 and December 31, 2020, the Company had an accounts receivable balance of
$1.3 million and $11.4 million, respectively, on the condensed consolidated balance sheet
related to the Procurement Contract.
In April 2021, the Company announced that the DoD had notified the Company that it will discontinue funding for the Phase 3 segment
trial of INO-4800 in the United States, while continuing to fund the completion of the ongoing Phase 2 segment.
Pg 31 In February 2021, Geneos completed a second closing of the Series A-1 preferred stock financing, in which the Company did not participate. Following this transaction, the Company held approximately 35% of the outstanding equity, on an as-converted to common stock basis.
The Company continues to exclusively license its SynCon® immunotherapy and CELLECTRA® technology platform to Geneos to be used in the field of personalized, neoantigen-based therapy for cancer. The license agreement provides for potential royalty payments to the Company in the event that Geneos commercializes any products using the licensed technology. The Company is not obligated to use any of its assets to fund the future operations of Geneos.
Pg 47 We have obtained Orphan Drug Designation from the FDA for INO-3107 for the treatment of recurrent respiratory papillomatosis. We have sought and may continue to seek Orphan Drug Designation for one or more of our other product candidates, including but not limited to VGX-3100 for the treatment of HPV-16-/18- associated anal dysplasia, although we may be unsuccessful in doing so.
Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. In the United States, Orphan Drug Designation entitles a party to financial incentives such as tax advantages and user fee waivers. Opportunities for grant funding toward clinical trial costs may also be available for clinical trials of drugs for rare diseases, regardless of whether the drugs are designated for the orphan use. In addition, if a product that has Orphan Drug Designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same product for the same indication for seven years, except in limited circumstances.
Orphan Drug Designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.
Tax reform legislation enacted in 2017 reduced the amount of the qualified clinical research costs for a designated orphan product that a sponsor may claim as a credit from 50% to 25%. This reduction could further limit the advantage of, and may impact our future business strategy with respect to, seeking the Orphan Drug Designation.
On positive interim readout of 1H22 RRP, Ino could sign a Collaboration and Licensing Agreement with upfront money and milestone payments before starting P3.
1/7/22 Overall Status: Recruiting => Active, not recruiting
The open-label, multicenter INO-3107 Phase 1/2 trial is currently open to enrollment to recruit up to 63 subjects and will evaluate the efficacy, safety, tolerability, and immunogenicity of INO-3107 in subjects who have required at least two surgical interventions per year for the past three years for the removal of associated papilloma(s). For this study, adult subjects will first undergo surgical removal of their papilloma(s) and then receive four doses of INO-3107, one every three weeks. The primary efficacy endpoint will be a doubling or more in the time between surgical interventions following the first dose of INO-3107 relative to the frequency prior to study therapy.
RRP is a rare disease caused by the human papillomavirus (HPV) types 6 and 11 infections, a condition that causes non-cancerous tumor growths leading to life-threatening airway obstructions. The disease is currently incurable and is mostly treated by surgery, which temporarily restores the airway. The majority of tumors are recurring, necessitating repeated surgery and severely impacting the quality of life for those living with the disease. Earlier this year, the US Food and Drug Administration (FDA) granted INO-3107 Orphan Drug Designation.
11/23/21 INOVIO Announces Dosing of First Subject in Phase 1/2 Clinical Trial for INO-3107, its DNA Medicine to Treat a Rare Disease Recurrent Respiratory Papillomatosis (RRP)
“In fact, we think VGX-3100 (HPV program) and INO-5401 (GBM program) will be the main value drivers for Inovio moving forward, and while we don’t expect any catalysts for these programs in 1H22, we expect readouts for INO-4500 in Lassa fever and INO-3107 in RRP in 1H22 to further de-risk the platform and add momentum to the story,” he added.
Dr. Ted Mau, Assistant Professor of Otolaryngology, Head and Neck Surgery, at UT Southwestern Medical Center, and lead investigator for INOVIO's RRP Phase 1/2 clinical trial, said, "As a surgeon, I have had patients who have required dozens of surgeries and are looking at many more during their lifetimes. This new systemic therapy is specific for RRP and has the potential to meaningfully alter the treatment paradigm for patients living with this disease."
https://clinicaltrials.gov/ct2/history/NCT04398433?A=20&B=21&C=merged#StudyPageTop
Elon Musk cheers on Justice Department probe of short sellers
The DOJ probe, according to The Wall Street Journal, is focusing on alleged instances of so called “spoofing” and “scalping.” Spoofing involves illegally using fake orders to pump or crash a stock price while scalping refers to when activist investors close out their positions without disclosing that move.
Muddy Waters Research founder Carson Block, a vocal critic of Musk’s who has shorted Tesla stock, is reportedly among the investors who have been served search warrants by federal investigators in the short-seller probe.
Block said in a statement to the Journal: “I’ve been saying for several years that it is critical for all stakeholders in the ecosystem to develop sophisticated data analysis capabilities to detect problematic trading. It’s dangerous to outsource these analyses to nonpractitioners.”
The New York Times reported last year that Block was moving on from shorting the electric vehicle giant. In a letter the Times obtained, Block explained his decision to allies by saying “the market cap, the luster, the élan of Elon, is still there.”
Andrew Left, another one-time Tesla short, had his computers seized by federal agents, according to Bloomberg. Left said in 2020 that he was shorting the company’s stock.
Musk’s war with short sellers goes beyond advocating for his company. He spoke out against shorts during the GameStop stock frenzy last year, when large groups of retail investors on Reddit helped pump the stock up 1,500% in two weeks.
“u can’t sell houses u don’t own u can’t sell cars u don’t own but u *can* sell stock u don’t own!? this is bs — shorting is a scam legal only for vestigial reasons,” Musk said in a tweet in January 2021.
Omicron booster in ancestral strain vaccinated mice augments protective immunities against both the Delta and Omicron variants
https://www.biorxiv.org/content/10.1101/2022.02.19.481110v1.full.pdf
DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron- matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-reactive immunities.
UK Lassa fever death shows rise in global infectious disease risk
https://www.tribuneindia.com/news/health/uk-lassa-fever-death-shows-rise-in-global-infectious-disease-risk-371568
“The three confirmed cases of the potentially deadly Lassa fever in the UK, now very sadly including one death, are a stark reminder of our interconnected world and the need to continue to invest in outbreak preparedness and response efforts,” Melanie Saville, the director of vaccine development at the Coalition for Epidemic Preparedness Innovations (CEPI), was quoted as saying.
“Emerging infectious diseases are increasing in prevalence, severity and spread as a result of climate change, global transportation and human encroachment into previously isolated areas,” she added.
The growing threat posed by deadly infectious diseases, Saville said, underlines the “urgent need for vaccine”.
CEPI is now advancing the development of six Lassa fever vaccines. Three of these—developed by Inovio Pharmaceuticals, the International Aids Vaccine Initiative (IAVI), and Themis Bioscience—are the first in the world to enter clinical trials, the report said.
Further, to produce a licensed Lassa vaccine for routine immunisation, the largest-ever Lassa fever study, called Enable, has been launched in west Africa with more than 20,000 participants, the report said.
Some scientists have raised concerns over the need to increase funding for the development of vaccines for other deadly infectious diseases.
Dame Sarah Gilbert, one of the creators of the Oxford/AstraZeneca vaccine, had warned in October that her team was struggling to raise the money needed to develop vaccines against diseases, including Lassa fever.
Meanwhile, the UK government this week committed 10 million pound funding for research into vaccines against deadly infectious diseases. The UK Vaccine Network will provide grants for 22 projects aimed at tackling severe illnesses in low- and middle-income countries.
They include 498,000 pound to DIOSynVax to develop its vaccine against Lassa fever, Ebola and Marburg virus disease, the report said.
From Reddit....Recently, Ai Weixin (Suzhou) Biopharmaceutical Co., Ltd. was awarded the advanced group of national science and technology system to fight against the new crown pneumonia epidemic, and the Ministry of Science and Technology issued a certificate to Ai Weixin.
According to the "Notice of the General Office of the Ministry of Science and Technology on Recommending Advanced Groups and Individuals in the National Science and Technology System to Fight the New Coronary Pneumonia Epidemic" (National Science and Technology Office Award [2021] No. 23), the science and technology departments (commissions and bureaus) of all provinces, autonomous regions and municipalities directly under the Central Government, Xinjiang The Science and Technology Bureau of the Production and Construction Corps and the State Council's Joint Prevention and Control Mechanism for Novel Coronavirus Pneumonia Epidemic Prevention and Control Mechanism Research Team selected and recommended by each special class unit, and the National Science and Technology System's Commendation Work Leading Group for Fighting the New Coronary Pneumonia Epidemic has researched and confirmed that the national science and technology system to be commended has fought against the new coronary pneumonia. There are 163 advanced groups in the epidemic, including a number of vaccine and drug research and development teams. Aidi Weixin (Suzhou) Biopharmaceutical Co., Ltd. finally won this honor, which is the recognition of Aidi Weixin by relevant departments .
Recently, the vaccine research and development special class of the joint prevention and control mechanism of the State Council's joint prevention and control mechanism for the new coronavirus pneumonia epidemic also sent a letter of thanks to Ai Weixin, thanking Ai Weixin for his great contribution to my country's new crown vaccine research and development in the past two years. It has been highly recognized by the party and the state.
The letter of thanks points out : "In the past two years, ( Suzhou) Biopharmaceutical Co., Ltd. has a high sense of political mission and responsibility, has the courage to take responsibility, is willing to pay, overcame difficulties, united and cooperated, and in hundreds of hard days and nights, with superb Business ability Actively carry out new crown vaccine research and development, so that China's vaccine research and development has always been in the world's first phalanx, seized strategic opportunities for China's epidemic prevention and control, and made great contributions to China's vaccine research and development, which has been highly recognized by the party and the country.
Since the outbreak of the new crown epidemic, Ai Di Weixin has always taken the strategic deployment of the party and the country as the highest task, and has worked hard to make my country's deoxyribonucleic acid (DNA) vaccine technology occupy the commanding heights of the world and make my country's new crown DNA vaccine research and development always in the world's first phalanx. So far, Aidi Weixin has established a comprehensive technology platform for the design and development of DNA vaccines, large-scale production processes, high-purity plasmid production, and new delivery technologies. The independent, independent and controllable aspects of risk prevention and control and advanced technology have honorably completed the phased mission.
The new crown DNA vaccine pGX9501 developed by Ai Weixin Biopharmaceuticals is a deoxyribonucleic acid vaccine based on circular DNA plasmids. It has completed Phase I and Phase II clinical studies in China and the United States, and is conducting Phase III clinical studies in multiple countries and centers around the world. , and was selected by the World Health Organization as the global new crown vaccine solidarity test variety, and sequential immunization clinical research with inactivated vaccines is also underway. At present, Aidi Weixin has established a GMP production line for the new crown DNA vaccine, obtained a vaccine production license, and has deployed dozens of patents related to the new crown vaccine around the world, targeting the known variants of the new coronavirus and potential future variants. Broad-spectrum vaccine candidates are also in full swing.
Indonesia relies heavily on China’s Sinovac vaccine. A new wave of infections puts it to the test
Indonesia has relied heavily on inactivated virus vaccines produced by China, which studies previously showed were less effective than mRNA shots.
On Wednesday, Indonesia hit a daily record high of more than 64,000 cases — superseding daily infections in the previous wave, which peaked just under 57,000 in July 2021.
Two medical doctors who spoke to CNBC argued that China-produced vaccines — such as the one developed by Sinovac Biotech which Indonesia has relied on most heavily — are still able to prevent severe illness and death.
Indonesia is going through a new wave of Covid infections, with daily cases hitting record highs last week.
The Southeast Asian country has relied heavily on inactivated virus vaccines produced by China, which studies previously showed were less effective than mRNA shots.
Messenger RNA, or mRNA, vaccines use genetic material to trigger the infection-fighting process in the body, while traditional vaccines use a dead or weakened virus to produce an immune response.
On Wednesday, Indonesia hit a daily record high of more than 64,000 cases — superseding daily infections in the previous wave, which peaked just under 57,000 in July 2021.
The country has reported 5.2 million cases of Covid-19 to date and at least 146,000 deaths since the start of the pandemic, according to the health ministry. It has the highest number of cases among Southeast Asian countries, Johns Hopkins data showed.
The latest surge in Indonesia’s Covid cases has put China-made vaccines to the test.
Two medical doctors who spoke to CNBC argued that China-produced vaccines — such as the one developed by Sinovac Biotech which Indonesia has relied on most heavily — are still able to prevent severe illness and death.
“That’s actually, I mean, the first and the main benefit of any kind of vaccine in the world,” said Dr. Dicky Budiman, a global health security researcher at Griffith University in Australia.
Being less effective is not the same as being ineffective, he told CNBC.
“If you received two doses or three doses of Sinovac or Sinopharm, those vaccines frankly are doing their job,” said Vin Gupta, an affiliate assistant professor at the Institute for Health Metrics and Evaluation, an independent global health research center at the University of Washington.
The shots don’t prevent infection, but are keeping people out of hospitals — “exactly what they should be doing,” he told CNBC’s “Street Signs Asia” last month, adding that the world has had wrong expectations of Covid vaccines.
Omicron threat
Before omicron emerged, studies showed the efficacy of Chinese vaccines was lower than that of mRNA shots, which reported more than 90% effectiveness.
The WHO said the Sinopharm vaccine’s efficacy against symptomatic Covid infections is 79%, while Brazilian researchers said the efficacy of Sinovac shots was 50%.
In April, the director of the China Centers for Disease Control, Gao Fu, was quoted by the Associated Press as saying that Chinese vaccines “don’t have very high protection rates.” He later said it wasn’t an admission that Chinese vaccines have a low protection rate, but that he was offering a scientific vision to improve vaccine efficacy, the Chinese state-run Global Times reported.
The UN health agency has approved both Sinopharm and Sinovac for emergency use.
As omicron spread in December, researchers from the University of Hong Kong found that the Pfizer-BioNTech vaccine, which uses the new mRNA technology, fared slightly better than Sinovac shots against the variant, but noted that both did not provide enough protection.
In that sense, all countries remain vulnerable to high case numbers, said Dr. Edhie Rahmat, who is executive director of Project HOPE Indonesia. Project HOPE, short for Health Opportunities for People Everywhere, is a global health and humanitarian relief organization.
He pointed out that the U.S. has administered mostly mRNA vaccines, which are seen to be more effective — but it’s still vulnerable to omicron. Cases surged in the U.S. in January as the variant swept through the country. Deaths spiked but remained lower than in previous waves.
Many developing countries around the world relied on Chinese-made Covid vaccines which are easier to transport and store compared to those developed by Pfizer or Moderna, which must be kept at subfreezing temperatures.
Budiman from Griffith University said countries should use any available vaccine that has been approved by the World Health Organization.
“If we wait [for] the messenger RNA, many people … will die during the delta wave,” he said.
He also said he hopes the world won’t see vaccines as “Chinese” or “Western,” but rather as “available tools” that we have and can use now.
Virus situation
Covid cases in Indonesia started rising rapidly in January and continue to climb. The WHO said in a Feb. 15 epidemiological report that infections in the country increased 68% from the week before.
Rahmat of Project HOPE said the increase in cases has come mainly from cities with high population density such as Bandung, Yogyakarta and the capital of Jakarta. However, the virus could spread further in suburban areas soon, he said.
Bed occupancy rates in hospitals are also rising. “This is a worrying situation. If the cases increase sharply in the coming weeks, there will be many people who need hospitalization, and the hospital surge capacity could be reached very soon,” he warned.
The good news, Rahmat said, is that Indonesians are more aware of tracing and testing now, and are taking initiative to get tested when they’re in close contact with confirmed cases.
The country is also better positioned now, given that vaccination rates have risen, he added.
Additionally, both doctors said people who recovered from an earlier strain of the virus may have some immunity, though they cautioned that the level of protection would wane within months.
However, Budiman said public health measures are not strong enough. He said that the testing capacity is not high enough, which means official figures on case numbers likely do not represent the full picture.
Some 50.64% of the population is fully vaccinated, according to Our World in Data. By comparison, neighboring Malaysia has fully vaccinated 78.54% of its population, while that figure is 56% in the Philippines.
Authorities in Indonesia rolled out boosters for the general public in January.
2/16/22 Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein, Emerging Microbes & Infections,
The mice were injected twice with a two-week interval via the intramuscular route (i.m.) with 25 µg of pVAX-S-WT, made from the wild-type sequence of the full-length spike protein of the SARS-CoV-2 (SARS-CoV-2/WH-09/human/2020/CHN), or with pGX9501 expressing a synthetic, optimized sequence of the SARS-CoV-2 full-length spike glycoprotein15. Electroporation was applied with the Cellectro2000™ device. Serum samples and spleens were collected 14 days after the second immunization.
https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2043727
This work was supported by the Chinese National Natural Science Foundation (81991492 and 82041039) and the National Key R&D Program of the Chinese Ministry of Science & Technology (2018YFC0840402) to B.Wang. We wish to thank Dr. Douglas Lowrie for proofreading this revised manuscript and Dr. Yiwei Zhong at Shanghai Medical College of Fudan University for her technical support.
The SARS-CoV-2 virus was found to mutate rapidly. Accordingly, the development of vaccines protecting people from different virus variants is urgently needed. The neutralizing antibodies induced by vaccines were found to have variable efficacies against the different SARS-CoV-2 variants, and efficacies declined over time, whereas the protection represented by CD8+ T cell immunity remained unchanged24. Peptide 2 is a highly conserved epitope among all variants and well-presented by MHC-1 of all HLA alleles across the globe. Thus, the conserved Peptide 2 should be suitable for evaluating COVID-19 vaccines for T cell response, particularly for the CD8 T cell-mediated functions. It is also possible to include such an epitope in new COVID-19 vaccines to induce a robust cellular response against all variants of SARS-CoV-2. A recent study confirmed that Peptide 2 probably has a strong cell-mediated immunological function in man; a 9-mer (YLQPRTFLL) peptide overlapped by Peptide 2 could induce a high level of IFN-? expression from PBMCs of patients who had recovered from COVID-19 and carried the HLA-A*02:01 allele29. The 9-mer peptide only showed a relatively good MHC-I binding ability in H-2Ld allele (STable 1), and it stimulated a weaker IFN-? T cell response than Peptide 2 in mice (Sfigure 2). In conclusion, our study utilized web-based tools to predict human MHC-I epitopes and found several sequences falling into the category. Among these, Peptide 2 (YYVGYLQPRTFLLKY) was not given the most decisive total TAP score in the prediction, but overall it simulated a more robust antigen-specific IFN-?-expressing CD8+ T response compared to the other predicted epitopic sequences. This epitope sequence is located at the end of NTD of the spike protein and is highly conservative among the currently known SARS-CoV-2 variants and recognizable with the diverse HLA alleles prominent in most world populations. This critical MHC-I epitope can be used to assess CMI induced by COVID-19 vaccines and maybe strategically incorporated into vaccine designs to enhance the prospect of viral elimination by vaccination.
The ACT-Accelerator is asking donor countries to contribute US$ 16.8 B of the $23.4 B total budget in immediate grant funding for Oct 2021 to Sept 2022 – with all funding figures rounded to the closest decimal. With $814 M of this $16.8 B already pledged, $16 B is now needed to close the immediate financing gap.
Closing this immediate $16 B financing gap would cover the most urgent work of the ACT-Accelerator’s constituent agencies, as set out in the initiative’s Strategic Plan and Budget, published in October 2021. It would cover procurement, research and development, product assessment, and rolling out vaccines, tests, and treatments, meeting the needs of low-income countries and the most vulnerable LMICs.
The aim is for the remaining $6.5 B of the $23.4 B budget to be self-financed by middle-income countries, using domestic resources to cover certain procurement needs,supported by multilateral development banks.
Separate to the ACT-Accelerator budget of US$ 23.4 billion, US$ 6.8 billion is needed for in-country delivery needs of vaccines and diagnostics, from a combination of domestic resources, multilateral development bank support, and further international grant financing support.
Closing the US$ 16 billion gap facing the ACT-Accelerator will enable the partnership to:
* in-country rollouts to get vaccines into arms, create a Pandemic Vaccine Pool of 600 million doses, support community engagement and cover ancillary costs for donations – contributing to countries’ national vaccination objectives towards the global target of 70% coverage in all countries by mid-2022
* Support clinical trials for treatments and vaccines, to help address variants of concern and initiate the development of broadly protective coronavirus vaccines.
https://www.who.int/news/item/09-02-2022-act-accelerator-calls-for-fair-share-based-financing-of-usdollar-23-billion-to-end-pandemic-as-global-emergency-in-2022
NVX-?CoV2373 ?stored 2–8 ?°C (6 months) or ?-?20? ?°C (two years???), Spike (pre-fusion)?, efficacy 86%, dose/interval? 2/21 days .
INO-4800 is stable at room temperature for more than a year, at 37°C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage. The ability to distribute INO-4800, and to license to global manufacturers, without the burden and expense of frozen cold-chain logistics, indicate the suitability of this DNA vaccine for international deployment at scale.
given its tolerability and immunologic profile to date, as well as lack of an anti-vector response, INO-4800 may also serve as a heterologous booster independent of the primary vaccination regimen. INO-4800 is composed of a precisely designed DNA plasmid that is administered intradermally followed by electroporation produce a well-tolerated immune response.
4.2. Therapeutic HPV Vaccination
Therapeutic HPV vaccines aim to restore or prime cell-mediated immunity through the induction of HPV-specific T-cell response.
J. Clin. Med. 2022, 11, 1101
10 of 29
HPV vaccines targeting E6 and E7 in HPV-related (pre-)cancers have been investigated, including genetic vaccines (e.g., DNA/RNA/virus/bacterial), protein-based, peptide- based, or dendritic-cell-based vaccines [151].
DNA vaccination forms an attractive approach for the induction of cellular immune responses, as these vaccines are very stable and tolerable for all patient populations and easy to produce and relatively cheap [153]. The disadvantages of DNA vaccines are their low transfection efficiency and restricted immunogenicity [154]. A few strategies facili- tating antigen delivery, processing, and presentation have been widely adopted to help increase the immunogenicity of HPV vaccines [151,155,156]. Clinical trials have reported on the enhanced immunization by electroporation-delivered DNA vaccine. Electropora- tion at the injection site can increase cell membrane permeability and enhanced nucleic acid uptake and subsequent immunogenicity [157]. In a phase I trial in patients with CIN3, vaccination with GX-1183 by electroporation elicited a significant E6/E7-specific IFN-?-producing T-cell response in all nine patients, and 7/9 (78%) of the patients had complete regression of their lesion and clearance of HPV DNA [156]. A Phase II study in a larger population found that 52% (33/64) of the patients had histopathologic regression of CIN3 [158]. Another electroporation-delivered vaccine, VGX-3100, elicited robust adaptive immune responses and provided complete histological regression for 49.5% (53/107) of the CIN2/3 patients [159]. Ex vivo immunological analyses demonstrated that the magnitude of the T-cell response against E6 was associated with clinical outcome. Currently, VGX-3100 is in a Phase III clinical trial (NCT03185013) and is being investigated in 201 patients with confirmed HPV-16/18-positive CIN2/3. Another vaccination strategy to enhance immu- nization is by DNA tattooing. This strategy showed an increased vaccine-specific T-cell response in comparison with classical intramuscular DNA vaccination in non-human pri- mates [160]. A recent phase I/II clinical trial performed by our group used DNA tattooing technique to deliver a genetically enhanced vaccine targeting E6 and E7 in patients with uVIN [153]. The vaccine was found to be well tolerated, and importantly, 6/14 patients showed an objective clinical response (43%; 14% CR, 29% PR). Systemic HPV-specific T-cell responses were observed in five out of the six responders. Moreover, in a similar patient population, lesion clearance was related to the magnitude of the HPV-specific response ex vivo after vaccination with HPV 16 synthetic long peptide [161–163].
In one of these studies, remarkable response rates were observed in patients with VIN upon vaccination with a synthetic long peptide vaccine encompassing the HPV 16 E6 and E7 oncoproteins [162]. At 12 months of follow-up, 15 out of 19 patients (78%) had a clinical response, with a complete response observed in 9 out of 19 patients (47%). These responses were accompanied by the induction of type-1 T-cell responses against E6 and E7. Results from a phase II study investigating the same HPV 16 synthetic long peptide vaccine in advanced or recurrent HPV-16-induced gynecological carcinomas were disappointing; monotherapy with this vaccine showed only weak T-cell responses and no clinical bene- fit [164]. The reason for this failure in late-stage cancer patients is likely due to high immune suppression in both the tumor and the associated lymph nodes. Therapeutic HPV vaccina- tion in combination with other treatment modalities (e.g., checkpoint inhibitors) is therefore needed in order to overcome immune suppression and establish effective anti-immune responses in HPV-related cancers. Indeed, in a phase II study (NCT02426892), the ISA101 synthetic long peptide vaccine in combination with nivolumab (anti-PD-1) resulted in a response rate of 33% (8/24) and median survival of 17.5 months in patients with incurable HPV-16-positive malignant neoplasms (22 oropharyngeal, one cervical, and one anal) [165]. Moreover, several ongoing basket trials are investigating HPV vaccines in combination with other immunotherapy agents in locally advanced or metastatic HPV-positive malignancies (NCT04432597, NCT03439085, NCT04287868).
Overall, for both CIN and uVIN patients, clinical efficacy of therapeutic vaccination was associated with the strength of the vaccine-induced immune response [153,156,159,161,162,166]. Although these results are encouraging, no therapeutic vaccines have been approved for
J. Clin. Med. 2022, 11, 1101
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clinical use in patients with HPV-related lesions of the cervix and vulva yet. In the case of PeIN, the usefulness of therapeutic vaccines has yet to be investigated.
Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis
Received: 20 January 2022 Accepted: 17 February 2022 Published: 19 February 2022
https://mdpi-res.com/d_attachment/jcm/jcm-11-01101/article_deploy/jcm-11-01101.pdf
Novavax bets fears over mRNA technology will give its Covid jab an edge
US biotech says its shot could alleviate vaccine hesitancy and calls on government to promote it
February 19, 2022 11:00 am by Jamie Smyth in Gaithersburg, Maryland
Novavax said its protein-based Covid-19 vaccine will be a strong competitor to the BioNTech/Pfizer and Moderna jabs despite its late arrival because of public concerns over the safety of its rivals’ messenger RNA technology.
But the US biotech, which began shipping its vaccine to Europe and Asia in January following months of long delays because of regulatory challenges, has called on Washington to do more to promote its vaccine, which has still not been authorised by US regulators.
“I would love to hear more public support from the US government and I don’t know whether they’ve been too involved in some of the other vaccines or they’ve been too busy,” said Stan Erck, chief executive of Novavax, adding US authorisation for its jab could happen “within weeks”.
The World Health Organization, the UK, EU and Australia are among almost a dozen countries and organisations to approve Novavax’s two-dose vaccine, which is the first product launched by the company in its 34-year history. Novavax plans to ship 2bn doses in 2022, which analysts’ forecast could generate $5bn in revenues — a transformational event for a biotech that has been a perennial loss maker.
But the company has struggled to provide data to US regulators that demonstrate it can manufacture jabs in a consistent manner. This has caused delays to the roll out of its two-dose vaccine, which clinical trials show has 90 per cent efficacy against symptomatic Covid-19. It followed the award of US government contracts worth $1.8bn to Novavax to develop its vaccine and supply 100m doses.
Erck told the Financial Times these problems had been resolved and Novavax would soon begin shipping doses to the US from its manufacturing partner, the Serum Institute of India. He said there is still plenty of demand for the company’s jab in high-income countries even though vaccination rates are high, citing contracts for 69m doses agreed with the EU in December.
“This puts a big stamp of approval on our vaccine in high-income countries,” Erck said, adding the company is in talks with US authorities about how many doses it would deliver and when.
Novavax said its jab could help tackle vaccine hesitancy in developed nations because it is made using a traditional vaccine production method rather than mRNA technology, a new platform that has become a target for misinformation by antivax campaigners. The company has also suggested its protein-based technology could provide more durable protection against Covid without a risk of myocarditis — a rate heart condition that has been linked to mRNA jabs.
Greg Glenn, Novavax’s president of R&D, said the mRNA vaccines have some “safety” and issues in terms of adverse side effects, which would make Novavax a particularly attractive option when Covid-19 becomes endemic.
“Myocarditis. I mean it really happens,” he told the FT.
“The assessment has been made today that the risk and the outcome of that, which is you know not infrequent, is balanced with the risk of getting Covid?.?.?.?But the presentation is pretty bad. People who have myocarditis- they have severe chest pain, it’s difficult for the family and 96 per cent get hospitalised.”
However, Novavax has not done a head-to-head study pitting its jab against either the BioNTech/Pfizer or Moderna vaccines to provide accurate data comparing safety and adverse reactions.
David Dowdy, an epidemiologist at Johns Hopkins School of Medicine, said the number one message is that existing data showed that all of the widely used vaccines are exceptionally safe.
“With products that are this safe, it’s more important to get people vaccinated than to haggle over small differences in safety,” he said.
Dowdy said the Novavax vaccine could be a game-changer in some lower-income nations as it does not need very cold storage — a factor that has hampered distribution of mRNA vaccines in Africa.
Novavax said it intends to win a race with its mRNA competitors to gain approval for a combined flu and Covid-19 shot, with a target date of 2024, and deliver on a pipeline of other respiratory drugs.
https://www.ft.com/content/636f289c-97dd-473a-a74a-69d639942558
INO 4800. 95% efficacy at room temperature storage! pg 14, Table 9
Int. J. Environ. Res. Public Health 2022, 19(4), 2392;
Brazil study
Received: 5 January 2022 / Revised: 9 February 2022 / Accepted: 15 February 2022 / Published: 18 February 2022
7.2.1. DNA Vaccine INO-4800 INO-4800 is a plasmid DNA vaccine developed by Inovio Pharmaceuticals (USA) for preclinical testing within the ferret model of COVID-19. This DNA vaccine encoding the S protein was delivered by electroporation [33]. INO-4800 was able to reduce viral load in non-human primates; rhesus macaque, used as model, that received two doses (1 mg) for 4 weeks of the DNA vaccine showed humoral and cellular immune responses after 13 weeks [38]. The vaccine s+howed effectiveness against both D614 and G614 SARS-CoV-2 variants [38]. The study of safety, tolerability, and immunogenicity of INO-4800 for COVID-19 was tested in healthy volunteers using SARS-CoV-2 spike glycoprotein as antigen.
https://www.researchgate.net/publication/358711697_Classical_and_Next-Generation_Vaccine_Platforms_to_SARS-CoV-2_Biotechnological_Strategies_and_Genomic_Variants
Possible News before or on 3/1/22
WHO-led clinical trial of INO-4800 to be unblinded as early as the end of March and would determine whether the WHO recommends it for use against COVID-19.
According to the WHO, research teams in Colombia, Mali, and the Philippines began recruiting volunteers for the Solidarity Trial Vaccines, which aims to "rapidly evaluate the efficacy and safety of promising new candidate vaccines against COVID-19," in late September 2021.
As of Dec. 22, 2021, over 11,500 people had registered to take part in the project, WHO data showed.
https://focustaiwan.tw/society/202202150024
Jan 31, 2022 INNOVATE Study has started Recruiting in Rwanda, Tunisia.
https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=16121
7117-ppl INNOVATE has completed enrollment in Brazil, Colombia, Philippines since 10/29/2021, in Mexico by now. Very high Omicron attack rate sped up cases.
https://clinicaltrials.gov/ct2/history/NCT04642638?A=9&B=10&C=merged#StudyPageTop
Advaccine provides 2 wk interim readout from homologous and heterologous 4800 trials
https://www.chictr.org.cn/hvshowproject.aspx?id=119337
Jan 31, 2022 INNOVATE Study has started Recruiting in Rwanda, Tunisia. Total Enrollment: 7,116
Name of recruitment centre Street address City Postal code Country
Center for Family Health Research KK 19 Av, No. 57, Kicukiro Kigali 780 Rwanda
Rinda Ubuzima research centre KG 11 Avenue No 47 P.O Box 4560 Kigali 4560 Rwanda
Hopital Militaire de Tunis 1008 Montfleury Tunis 1008 Tunisia
Hopital Militaire de Sfax Express Rocade Nr 11, Thyna Sfax 3029 Tunisia
Hospital Fattouma Bourguiba Rue du 1er juin 1955 Monastir 5000 Tunisia
Primary Outcome Phase 3: Percentage of Participants, (SARS-CoV-2 seronegative at baseline), With Virologically-confirmed COVID-19 Disease From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 Day 42 up to Day 393
https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=16121
https://covid19.trackvaccines.org/vaccines/17/#trial-pactr202110626944896
https://covid19.trackvaccines.org/country/colombia/
Key features of STV include:
mobile trial sites to enable reaching people in remote areas and achieve more equitable recruitment
interim analyses to identify better performing candidates and to eliminate those that are performing poorly against pre-specified statistical thresholds
long-term follow-up to increase the rigour of results and enable formal evaluation of efficacy vs. severe disease & duration of efficacy
Selection evaluation of pre-defined criteria, including:
their safety and proven potential for effectiveness
stability of the vaccine
demonstration that they can be stored and transported easily under normal conditions
availability - whether they can be produced quickly for global distribution
the ease with which they can be given to individuals (how the vaccines are given, the number of doses etc)
Key features of STV include:
mobile trial sites to enable reaching people in remote areas and achieve more equitable recruitment
interim analyses to identify better performing candidates and to eliminate those that are performing poorly against pre-specified statistical thresholds
long-term follow-up to increase the rigour of results and enable formal evaluation of efficacy vs. severe disease & duration of efficacy
who.int/emergencies/disease...
Selection evaluation of pre-defined criteria, including:
their safety and proven potential for effectiveness
stability of the vaccine
demonstration that they can be stored and transported easily under normal conditions
availability - whether they can be produced quickly for global distribution
the ease with which they can be given to individuals (how the vaccines are given, the number of doses etc)
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-trial-of-covid-19-vaccines
The Solidarity Trial Vaccine is registered at:
ISRCTN15779782
https://www.isrctn.com/ISRCTN15779782
Efficacy of COVID-19 Vaccination Among People Living With HIV in Taiwan, February 14, 2022
In a study of people living with HIV in Taiwan, COVID-19 vaccination was highly effective when implemented alongside non-pharmaceutical interventions.
COVID-19 vaccination is recommended, especially for immunocompromised people, but the efficacy of vaccines in people living with HIV is not fully understood.
One study, presented virtually during the 2022 Annual Conference on Retroviruses and Opportunistic Infection (CROI) by lead author Dr. Kuan-Yin Lin, sought to evaluate the effectiveness of single and 2-dose COVID-19 vaccination among Taiwanese adults living with HIV.
The study was conducted at the National Taiwan University Hospital from March 1-September 30, 2021. From April-August 2021, a large-scale, community-wide COVID-19 outbreak occurred in conjunction with strict non-pharmaceutical interventions, such as mask wearing and social distancing.
The prospective cohort study included adult participants living with HIV and without a history of COVID-19 infection. The 3131 included participants were all advised to receive 2 doses of a COVID-19 vaccine; the government-funded vaccination campaign allowed the participants to choose from the AZD1222, Pfizer-BioNTech, Moderna, and Medigen vaccines.
The investigators estimated the efficacy of COVID-19 vaccination in people living with HIV by comparing incidence rates among the unvaccinated, partially vaccinated, and fully vaccinated cohorts. Among the 3131 people living with HIV, 15.7% did not undergo vaccination, 73.6% received 1 dose of a COVID-19 vaccine, and 10.7% were fully vaccinated with 2 doses.
Of the vaccinated participants, 70.4% received the AZD122 vaccine, 23.9% received Moderna, 4.4% received Medigen. 99.9% were on antiretroviral therapy (ART), and 99.8% were men who have sex with men (MSM). The median CD4+ cell count of all participants was 627 cells/mm3.
The incidence rate of COVID-19 was 6.4 per 100000 people living with HIV in the unvaccinated group, 2.9 per 100000 among the partially vaccinated cohort, and 0 per 100000 in the fully vaccinated cohort. The adjusted incidence rate ratios yielded 53.4% protection for single-dose COVID-19 vaccination, and 99.9% vaccine efficacy for people living with HIV who received 2 doses.
The investigators concluded that vaccination was clinically effective among people living with HIV in an outbreak setting with staunch non-pharmaceutical interventions. The high vaccine efficacy suggests people living with HIV in the cART era should complete a primary COVID-19 vaccine regimen.
The study, “Effectiveness of COVID-19 Vaccination Among People Living With HIV During an Outbreak,” was presented virtually during the 2022 Annual Conference on Retroviruses and Opportunistic Infection (CROI).
WASHINGTON DC, 18 - 21 APRIL 2022
Apr 21 09:40
Inovio’s DNA COVID vaccine update
COVID & Beyond
Joseph Kim,Chief Executive Officer, Inovio Pharmaceuticals
Apr 21 09:00
Chair’s opening remarks
Emerging and Infectious Diseases
Stanley Plotkin,Emeritus Professor, University of Pennsylvania School Of Medicine
Apr 20 09:00
Chair’s opening remarks
Emerging and Infectious Diseases
David Weiner,VP, Director of Vaccine & Immunology Center, The Wistar Institute
https://www.terrapinn.com/conference/world-vaccine-congress-washington/agenda.stm?utm_source=email&utm_medium=pardot&utm_campaign=UK_10550_WVC+DC+2022_CONFPROM&utm_term=email
INNOVATE in Philippines Registry and 7 trial locations Started 10/29/21
Dr. Pablo O. Torre Memorial Hospital
Asian Hospital and Medical Center
Lung Center of the Philippines
Las Pinas Doctors Hospital
West Visayas State University Medical Center
University of the Philippines - Philippine General Hospital
Mary Johnston Hospital
https://registry.healthresearch.ph/index.php/registry?view=research&layout=details&cid=3894&fbclid=IwAR30EEccm--YIE-RdM_plUoZe678mCpf4i-E67JM41NT22GbSi5dB0MQ_L8
Item 7.01 Regulation FD Disclosure.
Inovio Pharmaceuticals, Inc., or INOVIO, announced that the World Health Organization, or WHO, confirmed to INOVIO on October 26, 2021 that INOVIO’s COVID-19 vaccine candidate, INO-4800, is one of two vaccines currently being tested in a large, international, randomized controlled Phase 3 clinical trial, called the Solidarity Trial Vaccines, being funded, sponsored, and conducted by the WHO. As stated by WHO, the Solidarity Trial Vaccines is designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines selected by an independent vaccine prioritization advisory group composed of leading scientists and experts.
INO-4800 was selected for inclusion in the Solidarity Trial Vaccines by the WHO’s independent vaccine prioritization advisory group out of approximately 20 candidate vaccines. Two additional vaccines are expected to enter the Solidarity Trial Vaccines once additional evidence and documentation has been reviewed and accepted as satisfactory by the independent vaccine prioritization advisory group.
The national principal investigators and their research teams in Colombia, Mali, and the Philippines have begun recruiting volunteers joining the trial at over 40 trial sites spread across the three countries. National research teams bring together experienced investigators well-versed in good clinical practice and the conduct of clinical trials.
The Solidarity Trial Vaccines aims to accelerate the evaluation of multiple promising candidate COVID-19 vaccines, contributing to the creation of a larger portfolio of vaccines needed to protect people from COVID-19 around the world. The trial has the additional potential to uncover second-generation vaccines with greater efficacy, possibly conferring greater protection against variants of concern, offering longer duration of protection, and/or using needle-free routes of administration.
Separately from the Solidarity Trial Vaccines, INOVIO is conducting a global Phase 3 COVID-19 vaccine trial of INO-4800, called INNOVATE, along with its partner Advaccine.
“As of January 3, 2022, eight hospitals and two community-based sites have already conducted the recruitment activities with a total of 5,901 have already been vaccinated with first dose and 3,840 participants have already completed the two-dose schedule of the first study vaccine,” she told the Manila Bulletin in an interview.
The lead investigators of the trial are Dr. Jodor A. Lim and Dr. Marissa M. Alejandria of the University of the Philippines (UP) Manila-Philippine General Hospital (PGH).
Guevara explained that the WHO-coordinated global study “Solidarity Trial Vaccines” is implemented locally through the project “Solidarity Vaccine Trial in the Philippines: Randomized Trial of Candidate Vaccines for COVID-19”.
She said recruitment of participants are ongoing on the following sites:
Philippine General Hospital (PGH)
Lung Center of the Philippines (LCP)
Makati Medical Center (MMC)
Quirino Memorial Medical Center (QMMC)
St. Luke’s Medical Center (SLCM)
Medical Center Manila (MCM)
Baguio General Hospital
San Juan De Dios Hospital (SJDH)
Sampaloc, Manila (community-based)
Crame, Quezon City (community-based)
The project team is eyeing to enroll 15,000 to 20,000 Filipinos aged 16 and above [40K worldwide in Mali, Colombia] to participate in the trial.
The enrolment of participants for the WHO STV started on Sept. 30, 2021.
Guevara said the study “will continue to run until the second quarter of 2022.”
According to the WHO, research teams in Colombia, Mali, and the Philippines began recruiting volunteers for the Solidarity Trial Vaccines, which aims to "rapidly evaluate the efficacy and safety of promising new candidate vaccines against COVID-19," in late September 2021.
As of Dec. 22, 2021, over 11,500 people had registered to take part in the project, WHO data showed.
Chen said the validation of the Medigen vaccine following the clinical trial would further enhance the company's collaboration with the WHO, which has been working to make more vaccines available and accessible through its global vaccine sharing initiative, COVAX.
2/11/22 STATE STREET CORP. filed SCHEDULE 13G
9. AGGREGATED AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
13,300,430
11. PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW 9
6.32%
2/10/22 Vanguard filed SCHEDULE 13G
9. AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH REPORTING PERSON
11,039,313
11. PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW 9
5.25%
2/1/22 Blackrock filed SCHEDULE 13G
(9) Aggregate amount beneficially owned by each reporting person
18244914
(11) Percent of class represented by amount in Row 9
8.7%
https://ir.inovio.com/financials/default.aspx#sec
BioRxiv: Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates
We recently described the design, immunogenicity, and efficacy of INO-4802, a synthetic DNA vaccine expressing a pan-Spike immunogen aimed at inducing broad immunity across SARS-CoV-2 VOCs [17]. In a hamster challenge model, INO-4802 conferred protection following intranasal challenge with either the Wuhan-Hu-1, B.1.1.7, B.1.351, P.1, or B.1.617.2 (Delta) SARS-CoV-2 variants. Additionally, INO-4802 showed promise as a heterologous booster vaccine by enhancing humoral responses against VOCs in hamsters previously immunized with INO-4800. Here, we addressed the immunogenicity of INO-4800 and INO-4802 as booster regimens in rhesus macaques previously immunized with INO-4800 using clinically relevant dosing parameters.
Rhesus macaques receiving booster immunizations of either INO-4800 or INO-4802 showed a robust induction of humoral responses, supporting the use of either vaccine in a prime/boost regimen. Importantly, boosting of INO-4800-primed animals with INO-4800 or INO-4802 resulted in neutralizing antibody responses that were magnitudes greater compared to pre-boost levels. Both treatment groups induced humoral responses capable of neutralizing wild-type and several VOC pseudoviruses, suggesting broad protection among SARS-CoV-2 variants. Pseudovirus neutralizing activity against the Beta and Gamma variants trended higher in animals boosted with the heterologous INO-4802 vaccine compared to those receiving INO-4800, indicating potential for an enhanced level of protection against some emerging SARS-CoV-2 variants following boosting with the next-generation pan-SARS-CoV-2 vaccine.
Neutralizing antibody responses correlated with inhibition of ACE2 binding activity, further supporting the functional antibody responses following either a homologous or heterologous boost with synthetic DNA vaccine constructs. Levels of antibodies binding variant Spike proteins were also increased following the boost immunization in both treatment groups. Together, these data point to broad functional humoral responses following a boost with both the original INO-4800 and INO-4802 pan-SARS-CoV-2 DNA vaccines. The rapid boost in neutralizing antibody responses can likely be attributed to the maintenance of a memory B cell pool following the priming immunization. Similar increases in humoral responses are observed in COVID-19 convalescent individuals who later received SARS-CoV-2 mRNA vaccines [44]. Longitudinal analyses have also found that SARS-CoV-2-reactive memory B cell clones are stably maintained in convalescent COVID-19 patients for several months following infection [30, 45]. Memory B cell responses persist despite the natural decline of SARS-CoV-2-specific IgG binding titers, suggestive of high-quality and durable memory B cell responses [46].
Neutralizing antibody responses are predictive of immune protection against symptomatic SARS-CoV-2 infection [47], and as such, neutralizing antibodies are an important readout in the evaluation of SARS-CoV-2 vaccines [48–50]. Owing to the critical role of T follicular helper (Tfh) cells in providing help to maturing B cells in germinal centers, Tfh responses serve as a mechanistic indicator of neutralizing antibody responses in infection and vaccination, including for EUA SARS-CoV-2 vaccines [25–27, 51–53]. We observed a positive correlation between the frequency of circulating Tfh cells and functional antibody responses, further affirming the immunogenicity of SARS-CoV-2 DNA vaccine boosters in animals with existing vaccine-induced immunity.
Overall, the development of safe and effective booster vaccines will be critical in maintaining control of SARS-CoV-2 in the long term. Ideal treatment regimens should seek to expand immune coverage to emerging variants while maintaining immune responses to existing SARS-CoV-2 variants. Current focus has shifted to evaluating the cross-immunogenicity of booster vaccines against wild-type SARS-CoV-2 antigens and other VOCs and re-designing vaccines to investigate this important question. In this study, we report that the next-generation pan-SARS-CoV-2 vaccine INO-4802 boosts immune responses in animals primed with the wild-type-matched SARS-CoV-2 DNA vaccine INO-4800. These data support the immunogenicity and boosting capability of INO-4800 and INO-4802 in nonhuman primates, which may have broader application in the clinical setting.
https://www.biorxiv.org/content/10.1101/2021.10.27.466163v1.full
Open Forum Infectious Diseases: Design and Immunogenicity of a Pan-SARS-CoV-2 Synthetic DNA Vaccine 12/4/21
Vaccines matching single VOCs, like pB.1.351 and pWT, elicit responses against the matched antigen but have reduced cross-reactivity. Presenting a pan-SARS-CoV-2 approach, INO-4802 may offer substantial advantages in terms of cross-strain protection, reduced susceptibility to escape mutants and non-restricted geographical use.
Background
First-generation COVID-19 vaccines are matched to spike protein of the Wuhan-H1 (WT) strain. Convalescent and vaccinee samples show reduced neutralization of SARS-CoV-2 variants of concern (VOC). Next generation DNA vaccines could be matched to single variants or synthetically designed for broader coverage of multiple VOCs.
Methods
The synthetic consensus (SynCon®) sequence for INO-4802 SARS-CoV-2 spike with focused RBD changes and dual proline mutations was codon-optimized (Figure 1). Sequences for wild-type (pWT) and B.1.351 (pB.1.351) were similarly optimized. Immunogenicity was evaluated in BALB/c mice. Pre-clinical efficacy was assessed in the Syrian Hamster model.
Results
INO-4802 induced potent neutralizing antibody responses against WT, B.1.1.7, P.1, and B.1.351 VOC in a murine model. pWT vaccinated animals showed a 3-fold reduction in mean neutralizing ID50 for the B.1.351 pseudotyped virus. INO-4802 immunized animals had significantly higher (p = 0.0408) neutralizing capacity (mean ID50 816.16). ID50 of pB.1.351 serum was reduced 7-fold for B.1.1.7 and significantly lower (p = 0.0068) than INO-4802 (317.44). INO-4802 neutralized WT (548.28) comparable to pWT. INO-4802 also neutralized P.1 (1026.6) (Figure 2). pWT, pB.1.351 or INO-4802 induced similar T-cell responses against all variants. INO-4802 skewed towards a TH1-response. All hamsters vaccinated with INO-4802 or pB.1.351 were protected from weight loss after B.1.351 live virus challenge. 4/6 pWT immunized hamsters were completely protected. pWT immunized hamsters neutralized WT (1090) but not B.1.351 (39.16). INO-4802 neutralized both WT (672.2) and B.1.351 (1121) (Figure 3). We observed higher increase of binding titers following heterologous boost with INO-4802 (3.6 – 4.4 log2-fold change) than homologous boost with pWT (2.0 – 2.4 log2 fold change)
https://academic.oup.com/ofid/article/8/Supplement_1/S391/6450079
Clarification on 2022/02/16 media reports. Provided by: Medigen Vaccine Biologics Corporation
1.Date of occurrence of the event:2022/02/16
2.Company name: Medigen Vaccine Biologics Corp.
3.Relationship to the Company (please enter "head office" or
"subsidiaries"):head office
4.Reciprocal shareholding ratios:N/A
5.Name of the reporting media:Economic Daily News 2022/02/16 C04
6.Content of the report:Charles Chen, the President of MVC (6547) said
yesterday (02/15), MVC is also conducting the immuno-bridging phase 3
clinical trial in EU. The result is also expected to be released in the
2nd quarter of 2022.
7.Cause of occurrence:
After consultation with European Medicines Agency (EMA) and considering
the difficulty of recruiting subjects due to high vaccine coverage rate in
EU, MVC will submit the clinical trial results conducted in non-EU country
to EMA for review. If there is a specific progress, it will be announced
in accordance with the regulations.
8.Countermeasures:None
9.Any other matters that need to be specified:
New drug development requires long process, vast investments and with no
guarantee in success which may pose investment risks. The investors are
advised to exercise caution and conduct thorough evaluation.
Disclaimer
Medigen Vaccine Biologics Corporation published this content on 16 February 2022 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 16 February 2022 06:13:02 UTC.
https://m.marketscreener.com/quote/stock/MEDIGEN-VACCINE-BIOLOGICS-45428599/news/Medigen-Vaccine-Biologics-Clarification-on-2022-02-16-media-reports-39483846/
Thermo Fisher dishes up $40M for Pennsylvania facility expansion, creating more than 100 jobs
by Fraiser Kansteiner | Feb 15, 2022 12:59pm
Thermo Fisher Scientific, plowing ahead on a more-than half-a-billion-dollar bioprocessing expansion, has telegraphed the next leg of its single-use technologies overhaul.
The company is plugging $40 million into an upgrade of its single-use technology manufacturing facility in Millersburg, Pennsylvania. The expansion–part of a long-term, $650-million investment Thermo Fisher unveiled last year–will tee up a new, 47,000-square-foot warehouse at the site, plus 100 new hires, the company said Tuesday. Thermo Fisher says it expects the site to employ more than 1,000 workers once it’s fully renovated by the middle of 2023.
Single-use technologies are increasingly being used in the development of biologic drugs and vaccines, Thermo Fisher noted in a release. The PA expansion will “add significant capacity to continue providing the biopharma industry with the technology and materials needed to assist in developing new vaccines, cancer treatments and breakthrough therapies for other conditions,” the company added.
Since the start of the pandemic, Thermo Fisher’s Millersburg site has been involved with more than 20 pharmaceutical partners to develop therapies and vaccines, the company said. The site currently employs more than 900 people, 200 of whom joined over the past three years, a Thermo Fisher spokesperson told Fierce Pharma.
“During the pandemic, our colleagues in Millersburg and around the world answered the call for increased production,” Mitch Kennedy, president of single-use technologies at Thermo Fisher Scientific, said in a statement. “Our expanded bioprocessing capabilities will ensure that we can continue to deliver essential supplies to our customers as demand surges.”
Thermo Fisher picked up its Millersburg facility back in 2015. Over the past two years, the company has “expanded and modernized” the plant’s warehouse and cleanrooms, Thermo Fisher said in its release.
Thermo Fisher’s wide-ranging bioprocessing investment, meanwhile, is meant to lock up “flexible, scalable and reliable” bioprocessing capacity for critical materials used in new and existing biologics and vaccines, including those for COVID-19. The capital investment originally totaled $600 million, but that figure rose to $650 million in September, when Thermo Fisher drew back the curtain on plans for a dedicated single-use technologies plant in Nashville.
That facility is set to become one of the world’s largest single-use manufacturing sites, Thermo Fisher has said, and it’s expected to more than double the company's single-use capacity. The first phase of the Nashville plant’s construction is expected to wrap up in this year’s second quarter, Thermo Fisher added.
Outside of Nashville, the multi-million-dollar spend is designed to boost single-use production capacity at sites in Utah, the United Kingdom, Singapore and China, Thermo Fisher said last year. Thermo Fisher's 115,000-square-foot single-use technologies manufacturing facility in Singapore has already opened for business, Thermo Fisher's spokesperson noted.
2/16/22 Medigen vaccine passes Paraguay trial, earns EUA
GLOBAL APPROVAL: Medigen is now waiting for the results of the WHO’s clinical trial evaluating the effectiveness of vaccines from around the world
The locally developed Medigen COVID-19 vaccine has successfully completed a phase 3 clinical trial in Paraguay and received emergency use authorization (EUA) from the South American nation.
The Taiwanese vaccine manufactured by Medigen Vaccine Biologics Corp (????) was hailed by Taiwanese experts as an important milestone for domestically produced vaccines.
Medigen’s vaccine has been gaining recognition from international institutions. It has been included in the WHO’s Solidarity Trial Vaccines program and received a US$2.3 million grant from the Coalition for Epidemic Preparedness Innovations to conduct a mix-and-match trial.
A double-blind, randomized study was used in the clinical trial in Paraguay to compare Medigen’s vaccine with that made by AstraZeneca, Taiwan Immunization Vision and Strategy (????????) chairman Huang Yu-cheng (???) said.
The results of the trial were similar to data collected from the phase 2 trial conducted in Taiwan.
Infectious-disease expert Lee Ping-ing (???) said that he was not surprised by the results and believes that Medigen’s vaccine would be approved by more nations.
Lee said that he hoped Taiwanese vaccines would no longer be politicized, but be generally accepted by Taiwanese.
Medigen is now waiting for the results of the WHO’s Solidarity Trial Vaccines clinical study, which evaluates the effectiveness of vaccines from around the world.
If the trial proceeds as scheduled, the results are expected by the end of next month or in early April, Medigen chief executive officer Charles Chen (???) said.
The company already has capacity to manufacture more than 100 million doses in preparation for a shift from domestic to international markets, he said.
The pandemic has offered an opportunity for domestic manufacturers to develop vaccines and for Academia Sinica to improve its mRNA-related technologies, Huang said.
The experience gained and the growth in research and development would hopefully lead to quicker responses to future pandemics, he said.
WHO-led clinical trial of Medigen COVID-19 vaccine to be unblinded
02/15/2022 10:07 PM
We will hear about Inovio much sooner than we thought.
Taipei, Feb. 15 (CNA) The Taiwanese vaccine maker, Medigen Vaccine Biologics Corp., said Tuesday that a World Health Organization-led (WHO) clinical trial of its COVID-19 vaccine could be unblinded in March at the earliest.
The Medigen COVID-19 vaccine, a protein subunit vaccine, is currently being tested under the WHO's Phase 3 Solidarity Trial Vaccines program.
At a press conference, the Taiwanese company's Vice Chairman and CEO Charles Chen (???) said that unblinding of the clinical trial could take place as early as the end of March and would determine whether the WHO recommends the Medigen vaccine for use against COVID-19.
According to the WHO, research teams in Colombia, Mali, and the Philippines began recruiting volunteers for the Solidarity Trial Vaccines, which aims to "rapidly evaluate the efficacy and safety of promising new candidate vaccines against COVID-19," in late September 2021.
As of Dec. 22, 2021, over 11,500 people had registered to take part in the project, WHO data showed.
Chen said the validation of the Medigen vaccine following the clinical trial would further enhance the company's collaboration with the WHO, which has been working to make more vaccines available and accessible through its global vaccine sharing initiative, COVAX.
The WHO has so far issued an emergency use listing for 10 COVID-19 vaccines.
He added that WHO recognition would also facilitate the vaccine brand's expansion in the Central and South American as well as Southeast Asian markets, as it will increase the possibility of the Medigen vaccine being granted emergency use authorization (EUA) by other countries.
Chen noted that the company had planned to supply its vaccine globally, and that it would aim to produce up to 100 million doses by the end of this year.
Meanwhile, Taiwan's Health and Welfare Minister Chen Shih-chung (???) said at a press briefing Tuesday that the government is considering donating part of its stock of approximately 3 million Medigen doses to other countries.
Currently, only Taiwan, Paraguay and the East African territory of Somaliland, have granted EUAs for the Medigen vaccine. In December 2021, Taiwan donated 150,000 Medigen doses to Somaliland to assist the territory in its efforts to combat the pandemic.
The National Directorate of Sanitary Surveillance (DINAVISA), of the Republic of Paraguay, granted this February 14 the emergency use authorization (EUA) to the Taiwanese vaccine against COVID-19 MVC-COV1901, produced by the biotechnological laboratory Medigen Vaccine Biologics Corporation (MVC), for application in adults from 18 years of age.
The certification ceremony was held at the Ministry of Public Health and Social Welfare, with the presence of the Minister, Dr. Julio Borba; the director of the DNVS, QF María Antonieta Gamarra; the director of the PAI, Dr. Héctor Castro; as well as the ambassador of the Republic of China (Taiwan), Mr. José Han; Project Manager, Medigen Vaccine Biologics Corporation (MVC), Mr. Evan Tu; the legal representative of MVC, Dr. Gabiela Horvath; and other authorities.
It is important to note that, in order to grant this approval, a team of professionals from the National Sanitary Surveillance Directorate carried out an exhaustive evaluation and inspection of the Medigen laboratories in Taiwan, whose establishment was certified for compliance with the requirements of good manufacturing and control practices (GMP).
It is worth mentioning that the results of the clinical studies of the MVC-COV1901 phase 3 vaccine in Paraguay showed that it meets the required requirements in terms of safety, tolerability and high immunogenicity, giving the conclusion to authorize its emergency use. The criteria for granting emergency use followed the international guidelines of the World Health Organization (WHO).
The MVC-COV1901 vaccine was developed from a traditional protein subunit platform, in collaboration with the US National Institutes of Health (NIH). Its profile is with a two-dose intramuscular application format, with an interval of 4 weeks between both doses, and its storage temperature is from 2 to 8 °C.
The MVC laboratory is certified by the health authority of the Taiwan Food and Drug Administration (TFDA), which is based on the PIC's Guides for Good Manufacturing Practices and Good Storage and Distribution Practices. The MVC-COV1901 Vaccine has the emergency use certificate granted by the TFDA on July 19, 2021 and, currently, in Taiwan it is used as a reinforcement or booster dose.
It is emphasized that the DNVS will continue to monitor the safety of the vaccines used in the country, to ensure that these products always meet local and international standards of safety and efficacy.
A Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Compared With AZD1222 Against COVID-19 in Adults
The primary objective of the study is to measure the anti-SARS-CoV-2 neutralizing antibody titers in adult participants so as to demonstrate immunogenic superiority of MVC-COV1901 to the active control, AZD1222 vaccine, in terms of the GMT ratio of neutralizing antibodies at 14 days after the second dose of study intervention. This study also assesses the safety and tolerability of the study intervention and explores the immunogenicity in terms of anti-S IgG as well as the potential efficacy of MVC-COV1901 in preventing COVID-19.
Locations: Paraguay
Hospital Fundación Tesai
Ciudad del Este, Paraguay
Hospital de Clinicas - Facultad de Ciencias Médicas, Universidad Nacional de Asunción
San Lorenzo, Paraguay
https://clinicaltrials.gov/ct2/history/NCT05011526?A=2&B=3&C=merged#StudyPageTop
35 dead and 234 Serious AE by Medigen after 1.4Million doses, as at Dec 6, 2021.
Source: Taiwan CDC VAERS Database.
Certain countries as Paraguay, 7,274,164 ppl only require a very small 934 ppl P3 immunobridging for EUA, in which a vaccine's effectiveness is inferred through a comparison of neutralizing antibodies generated rather than actual clinical results in the field. Ino could do the same to expedite the EUA. CD4+, CD8+ T cell responses should also be the important metrics.
The 40K ppl WHO’s Solidarity Vaccine Trial is a head-2-head comparison, also measures Percentage of Participants, (SARS-CoV-2 seronegative at baseline), With Virologically-confirmed COVID-19 Disease [ Time Frame: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2].
Potentially Big News for INO-4800: Medigen COVID-19 vaccine receives EUA in Paraguay
02/14/2022 11:28 PM
Taipei, Feb. 14 (CNA) A COVID-19 vaccine made in Taiwan by Medigen Vaccine Biologics Corp. has received emergency use authorization (EUA) in Paraguay after the unblinding of a Phase 3 clinical trial conducted in the South American country, the company said in a statement Monday.
The Phase 3 trial in Paraguay sought to test the Medigen vaccine's effectiveness by comparing the amount of neutralizing antibodies it generated in trial participants against those generated by another vaccine, in this case the AstraZeneca vaccine.
The company said the trial, which finished with 934 people getting two doses of one of the two vaccines, found that the Medigen vaccine generated 3.7 times as many neutralizing antibodies as its AstraZeneca counterpart, meeting the standard for "superiority."
That result was similar to the results obtained in Taiwan last year, when the Medigen vaccine became the first (and to date the only) domestically produced vaccine to receive EUA in Taiwan, the company said.
In terms of safety, no serious reactions to the Medigen vaccine were reported among any of the trial participants, and fewer than 1 percent reported getting a fever, according to Medigen.
Paraguay is only the second country in the world to give the Medigen vaccine an EUA, though it is currently undergoing reviews in several other countries and is being tested under the World Health Organization's Phase 3 Solidarity Trial Vaccines program.
When it received an EUA in Taiwan in June 2021, it was the first COVID-19 vaccine in the world to be approved through the process of immunobridging, in which a vaccine's effectiveness is inferred through a comparison of neutralizing antibodies generated rather than actual clinical results in the field.
https://focustaiwan.tw/society/202202140029
2/11/22 Lassa fever: Is this a sign of the new pandemic era?
Two Britons have been diagnosed with the virus that causes bleeding eyes and facial swelling – and it could be evidence of a changing world
Just hours after Boris Johnson unveiled plans to lift all Covid regulations in England on Wednesday, an alert warned of a new disease threat facing Britain: two people had been diagnosed with Lassa fever, a viral haemorrhagic disease similar to Ebola.
The pathogen – which is endemic in countries including Nigeria, Sierra Leone and Ghana – is less deadly than other haemorrhagic fevers, such as Ebola or Marburg. But it is nasty, killing roughly 15 per cent of those who are hospitalised.
Symptoms of Lassa start gradually, with fever and malaise, and after a few days a headache, muscle pain and vomiting may kick in. In severe cases, the virus triggers facial swelling, fluid-filled lungs and intense bleeding from the eyes, nose and other orifices. As yet, there is no licensed vaccine and treatments are poor.
Lassa’s arrival in Britain, in travellers from West Africa, is highly unlikely to trigger a major outbreak – although scientists told The Telegraph to watch this space in the coming days. They would not elaborate, but it is possible a track and trace initiative will be launched, further cases announced or that there will be complications in the patients’ treatment.
“Fortunately, the virus is nowhere near as infectious as many other pathogens,” says Dr Michael Head, senior research fellow in global health at the University of Southampton. “While any Lassa cases within the UK are of concern, we won’t be seeing transmission on anything like the scale we have with the Covid-19 pandemic.”
Dr Head points to the reproduction (R) number, used to describe how many people each infected person passes a disease onto. For Lassa, this is estimated at between 1 and 1.6 – compared with around 3 for the original Wuhan Sars-Cov-2 strain. The more transmissible omicron variant has an R number as high as 12.
Certainly, you would be unlucky to catch the Lassa virus on a bus: unlike Covid, it spreads through direct contact with the bodily fluid of an infected person, or after contact with the urine or faeces of infected rats. As long as you were not sitting next to someone with it, there would be little cause for concern.
But, as the acute phase of one epidemic finally appears to wane - at least for now - Lassa’s re-emergence in Britain is a stark reminder that the world is entering a “new pandemic era”, as Prof Anthony Fauci, America’s top infectious disease expert, warned in August 2020.
Pandemics are nothing new - humanity has been battling infectious diseases for centuries. In 430 BC, roughly 100,000 people died in what is known as the ‘Plague of Athens’, which heralded the end of the city’s Golden Age.
Almost a century later, the Justinian plague wiped out almost half of the global population, while Athenian historians claimed the third-century Plague of Cyprian, also thought to be a haemorrhagic fever like Lassa, killed up to 5,000 a day at the peak of the outbreak. The world has since been hit by tuberculosis, yellow fever, cholera and the Spanish flu, to name but a few.
But the idea of a pandemic era is new - it suggests that major pandemics may no longer be once-in-a-century events. Six months before the emergence of Sars-Cov-2, Dr Mike Ryan, director of emergencies at the World Health Organisation (WHO), warned the world was entering a “new normal”, when several “high-impact” disease outbreaks occur simultaneously.
Experts point to environmental changes that make it more likely that viruses will “spill over” to humans and lap the globe. This includes booming population growth, the development of previously undeveloped nations, the growth in the international trade in wildlife and widespread travel.
But the next pandemic may not look like Covid-19. Alongside Lassa fever, the WHO’s list of priority pathogens with pandemic potential includes Crimean-Congo haemorrhagic fever (CCHF), Ebola and Marburg.
“As we come out of one pandemic, we must still look for the next pathogens,” says Dr Tom Fletcher, an infectious disease specialist at the Liverpool School of Tropical Medicine.
In terms of haemorrhagic viruses, he adds, there are gaping holes in our knowledge and our ability to respond.
“As well as not having the right drugs or diagnostics, we don’t really understand how these diseases work, or what it is that causes patients to bleed,” Dr Fletcher says, “…but if we understand this, we can target treatment and improve the analysis of new diagnostics.
“The risks are going to persist going forward, they’re not going away – and we will see cases,” he adds. “And therefore we have to prioritise and fund key research.”
Dr Fletcher points to a conference set to take place in the Ivory Coast next week, where scientists will discuss how to design and enact trials for new treatments. But funding is lacking, so conclusions will be “theoretical”. “There is a complete dearth of funding for good drugs to treat Lassa and CCHF – that is criminal,” he says.
Yet the need is clear. In 2021, Turkey reported a record number of CCHF cases – a tick-borne disease with a fatality rate as high as 40 per cent – while Marburg, which is far deadlier, was detected for the first time in West Africa last summer. Ebola outbreaks, too, are on the rise – of the 12 outbreaks seen in the Democratic Republic of Congo since 1976, half have taken place since 2014.
That Lassa has now reached Britain’s shores is not surprising. The two confirmed cases, plus a third probable infection, are members of the same family and recently visited West Africa.
“The overall risk to the public is very low,” says Dr Susan Hopkins, chief medical adviser at the UK Health Security Agency. “We are contacting the individuals who have had close contact with the cases prior to confirmation of their infection, to provide appropriate assessment, support and advice.”
Although the last infections were detected here in 2009 – with eight reported in total since 1980 – the UK has close travel ties with countries where there are outbreaks of Lassa every year. So far this year, Nigeria alone has seen 211 confirmed cases and 40 deaths.
The disease was first identified in 1969, but its true scale remains unknown. Each year, there are an estimated 100,000 to 300,000 cases of the disease and 5,000 deaths, but some 80 per cent of cases are thought to be asymptomatic.
The Coalition for Epidemic Preparedness (Cepi), an organisation that has funded several Covid vaccines, is leading a $26m (£19.2m) project in West Africa to understand the full scale of the disease.
Current knowledge is hindered by a lack of formal diagnosis and the broad range and severity of symptoms. Cases may also occur in remote regions where there is no testing. As a result, most experts believe the true toll of the disease is likely to be much higher than current estimates.
There is a treatment for the virus – ribavirin, an antiviral – but it has to be given early on to be effective. Cepi is funding six vaccines, two of which entered phase one trials in 2019, and another started human trials last year.
Cepi’s goal is to get a licensed vaccine for routine immunisation, and Dr Melanie Saville, the organisation’s director of vaccine research and development, says there “have been a number of positive developments” in the past few years. Continuing to focus on R&D is critical, she adds, because novel pathogens from the same family of viruses as Lassa could be even more contagious or deadly.
“It is important to remember that Lassa virus is just one of a number within the Arenaviridae viral family,” Dr Saville says. “Other novel viruses within this family could emerge in the future with greater transmissibility and/or fatality rates.”
As European nations move into the post-Covid phase, there is a fear we will forget the lessons of the past two years.
“There will be another pandemic just around the corner,” says Dr Head. “We just don’t know when“
2/11/22 The Philippines posted 3,788 coronavirus infections on Friday, the fourth straight day the tally fell below 5,000.
This brought the total to 3.63 million, the Department of Health (DoH) said in a bulletin. The death toll hit 54,854 after 72 more patients died, while recoveries rose by 5,652 to 3.48 million.
The agency said 14.7% of 32,795 samples on Feb. 9 tested positive for COVID-19, still above the 5% threshold set by the World Health Organization (WHO).
Of 91,147 active cases, 3,261 did not show symptoms, 83,145 were mild, 2,986 were moderate, 1,443 were severe and 312 were critical.
DoH said 97% of the latest cases occurred on Jan. 29 to Feb. 11. The top regions with new cases in the past two weeks were Metro Manila with 470, Western Visayas with 455, and Davao with 453. It added that 44% of new deaths occurred in February and 32% in January.
The agency said 726 duplicates had been removed from the tally, 449 of which were reclassified as recoveries and one was tagged as a death, while 52 recoveries were relisted as deaths. One laboratory failed to submit data on Feb. 9.
It said 34% of intensive care unit beds in the country had been used, while the rate for Metro Manila was 24%.
Earlier in the day, Health Undersecretary Maria Rosario S. Vergeire refuted a claim by researchers from the University of the Philippines that Manila, the capital and nearby cities were now at low risk from the coronavirus.
“Although cases in the National Capital Region are falling, our metrics shows that it is still under moderate risk, not low risk,” she told an online news briefing in mixed English and Filipino.
Metro Manila’s daily attack rate was 12.53, with a seven-day moving average of 886 per day, she said.
OCTA Research Group fellow Fredegusto P. David on Wednesday said the capital region was at low risk from the coronavirus.
“I don’t understand why our metrics don’t align,” Ms. Vergeire said. “It’s confusing people. DoH is the official source and we are using metrics that show NCR is still classified as moderate risk.”
OCTA uses data from DoH and the website of The Act Now Coalition, a nonprofit group founded by volunteers in March 2020.
Edsel T. Salvana, director of the Institute of Molecular Biology and Biotechnology at the National Institutes of Health-University of the Philippines Manila, said they consider the level of community transmission and vaccination rate, among other things, before classifying the risk level.
Meanwhile, Ms. Vergeire said the coronavirus is not yet endemic because infections have yet to stabilize.
She also said the government is preparing for an eventual shift to Alert Level 1, which will become the so-called new normal.
The Philippines is scrambling to vaccinate more people as it reopens the economy.
On Thursday, it took delivery of 3.4 million doses of Pfizer, Inc.’s coronavirus vaccines donated by the United States under a global initiative for equal access.
“As the largest contributor to COVAX, the United States has facilitated the delivery of more than 69 million vaccine doses [to the Philippines, including more than 28.5 million doses donated by the American people,” the US Embassy said in a statement on Friday.
Ms. Vergeire said the government’s two-day vaccination campaign on Feb. 10 to 11 would be extended until Feb. 18.
She said 662,318 vaccine doses were injected on the first day of the immunization drive, 442,236 of which were first doses and 219,972 were boosters. The government seeks to fully vaccinate 77 million people by end-March. The country has fully vaccinated 60 million people.
She said only four of 52,262 children aged 5 to 11 who were vaccinated against COVID-19 in 56 sites nationwide experienced minor adverse reactions.
Rajendra Prasad, the World Health Organization’s acting representative to the Philippines, said 2.5 million seniors have yet to be vaccinated.
“Vaccinating older people is one of the most impactful ways to save lives during this pandemic,” he separately told a televised news briefing. “We know that senior citizens are at high risk of developing severe disease, getting hospitalized and dying from COVID-19.”
Electroporation Instruments Market to Garner a Valuation of US$ 1,036.6 Million by 2027, at CAGR of 3.2% | Lonza Group,
SEATTLE, WASHINGTON, UNITED STATES, February 8, 2022 /EINPresswire.com/ -- The electroporation process is very safe and reproducible. Commercially available apparatus is easy to use and has an adjustable voltage that enables researchers to get consistent results. There are two basic types of electroporation devices: the capacitor discharge system and the true square wave generator. The capacitor discharge system generates a single exponentially decaying current pulse. While the true square wave device produces a single, roughly equal pulse of electricity, the true square wave instrument creates multiple rapid pulses.
The global electroporation instruments market is expected to record a CAGR of 4.4% during 2021-2028 and was estimated to be valued at US$ 769.0 million in 2021.
High prevalence of cancer is also expected to propel growth of the global electroporation instruments market over the forecast period. For instance, according to the study, ‘Trends in thyroid cancer incidence in India’, published in May 2018 in the Journal of Clinical Oncology, the incidence rate of thyroid cancer in India in women increased from 2.4 to 3.9 and in men from 0.9 to 1.3, a relative increase of 62% and 48% respectively during 2004/05 to 2013/14.
Moreover, approval and launch of new products is also expected to propel growth of the global electroporation instruments market over the forecast period. For example, in June 2020, MaxCyte launched ExPERT disposables line with R-1000 cuvette that can process a volume of up to one mL, or up to 200 million cells, and offers greater versatility for companies involved in drug discovery.
Initiatives to boost cancer treatment is expected to offer lucrative growth opportunities for players in the global electroporation instruments market. For example, in February 2021, the European Commission launched Europe's Beating Cancer Plan that establishes a new EU approach to cancer prevention, treatment, and care, starting with new technologies, research, and innovation.
Major players operating in the global electroporation instruments market are focused on adopting partnership strategies to enhance their market share. For example, in May 2020, Caribou Biosciences Inc. partnered with MaxCyte, Inc., a cell-based therapies and life sciences company, under which Caribou gained rights to use MaxCyte's Flow Electroporation technology and ExPERT platform to advance its CRISPR gene-edited, allogeneic T cell therapy program.
For example, in May 2021, Inovio Pharmaceuticals, announced to employ electroporation to open channels in cells, allowing the DNA-based vaccine against COVID-19 to enter the human body. The U.S. Department of Defense backed Inovio's approach with a US$ 71 million contract to scale up production of its electroporation device and other studies. Moreover, the Bill and Melinda Gates Foundation contributed US$ 5 million to the company as part of an effort to increase equitable access to COVID-19 vaccines.
https://www.einnews.com/pr_news/562633783/electroporation-instruments-market-to-garner-a-valuation-of-us-1-036-6-million-by-2027-at-cagr-of-3-2-lonza-group
2/10/22 Ai Di Weixin sprints to the Hong Kong Stock Exchange
https://min.news/en/economy/795adf980b883da78a602aca8b732c87.html
ISRCTN15779782
https://doi.org/10.1186/ISRCTN15779782
Solidarity trial of candidate vaccines against COVID-19
https://www.isrctn.com/ISRCTN15779782
Primary outcome measure
Virologically confirmed COVID-19 disease, through SARS-CoV2 RNA isolation and RRT-PCR amplification in oro-nasopharyngeal specimen, regardless of disease severity, at 14, 180, 365 days after the last dose.
Secondary outcome measures
Measured at dose 1, dose 2, 7, 180, and 365 days after dose 2:
1. Serious adverse events (SAEs), adverse events of special interest (AESIs) as requested, collected for all participants throughout the study.
2. Severe COVID-19 (as per WHO classification) and death with recently confirmed COVID-19.
3. COVID-19 and severe COVID-19 diagnosed starting 14 days after the final dose through the final study visit.
4. SARS-CoV-2-specific neutralization antibody, binding antibody and T-cell immune responses measured using blood test in a subset of participants at selected sites.
5. COVID-19 viral load and other disease progression biomarkers measured using blood test.
Target number of participants
The trial is endpoint driven, as the main analysis for each vaccine arm versus the concurrent shared placebo/control arm is triggered by occurrence of a total of 150 cases of COVID-19 across these two arms, at which point the results will be reported but blinded follow-up will continue. This fixed num-ber of 150 endpoints is set to provide sufficient power to detect a predefined target level of VE, reject-ing the initially specified null hypothesis that VE is < 30%. For example, for the 150-endpoint design noted above, where a 50:100 vaccine:placebo endpoint split just meets success criteria, if the 6-month COVID-19 attack rate in the placebo arm is 1-2%, and par-ticipants are enrolled evenly over 3 months, then a total evaluable sample size of about 20,000 per vaccine arm, with an equal number in the shared-placebo arm is expected to yield the needed end-points within 2 to 4 months after the median enrolment date.
Publication and dissemination plan
This international collaboration is coordinated through the World Health Organisation, which is also a sponsor of the trial. Any wholly reliable interim findings will be disseminated rapidly by the WHO. There will be group authorship recognizing the contribution of all national and local investigators and guided by the International Committee of Medical Journal Editors (ICMJE) recommendations. Alt-hough the writing committee will consist of the executive group and the WHO trial secretariat, authorship will include all steering committee members and local collaborators whose hospital, in the view of the national principal investigator, contributed substantially towards the trial.
Intervention
Four vaccine candidates selected for evaluation. Candidate vaccines are selected on a rolling basis by the WHO Working Group on vaccine prioritization
Trial entry, randomization: Once electronic data collection has been completed the volunteer automatically enters the trial and a random allocation of their trial vaccine is generated (by an algorithm that ensures eventual balance in the characteristics just recorded between each study vaccines and its placebos) and displayed. The volunteers will be randomly allocated either to placebo or to one of the study vaccines.
Follow-up: Each participant will be contacted weekly for 52 weeks for information as to whether any potentially relevant symptoms have arisen, with laboratory testing triggered if the report suggests COVID-19.
Adaptive design: A global Data Monitoring Committee will keep the accumulating safety results and major outcome results under regular review. Different candidate vaccines may be available or suitable to enter the trial at different times; for each candidate vaccine, the primary efficacy results are expected within 3-6 months of the vaccine entering the trial. By using a shared placebo/control group and a common Core protocol to evaluate multiple candidate vaccines in the trial, resources allocated to the evaluation of each candidate vaccine are judiciously saved while a high standard of scientific rigor and efficiency is ensured.
Add-on studies: Particular countries, or particular groups of sites, may want to collaborate in making further measurements or observations. These could be thought of as Phase 2b trials that are being conducted concurrently with the Phase 3 trial. However, while well-organised additional research studies of additional secondary and supportive endpoints, for which monitoring is valuable but optional at each study site include infection with SARS-CoV-2, trans-mission of SARS-CoV-2, and possible immunological markers as correlates of risk could well be valuable, they are not core requirements in every site.