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BERLIN, March 17 (Reuters) - Germany will lift most restrictions to contain the coronavirus despite infections hitting a record in the country on Thursday.
Chancellor Olaf Scholz said after talks with leaders of Germany's 16 states that a record of almost 300,000 infections in one day was not good news, but the easing of restrictions was justified given intensive care units were not overwhelemed.
As of March 20, requirements to wear a mask will be dropped in indoor places like schools and at supermarkets but will remain mandatory in medical clinics and care homes.
Germany's 16 states will have the power to impose restrictions if they identify hotspots where both infections and hospitalisations peak.
The German parliament has been debating a vaccine mandate but it could take weeks before any vote on the divisive measure.
MILAN, March 17 (Reuters) - Italy reported 79,895 COVID-19 related cases on Thursday, against 72,568 the day before, the health ministry said, while the number of deaths fell to 128 from 137.
Italy has registered 157,442 deaths linked to COVID-19 since its outbreak emerged in February 2020, the second-highest toll in Europe after Britain and the eighth highest in the world. The country has reported 13.65 million cases to date.
Patients in hospital with COVID-19 - not including those in intensive care - stood at 8,397 on Wednesday, down from 8,410 a day earlier.
There were 51 new admissions to intensive care units, increasing from 31 on Wednesday. The total number of intensive care patients were down to 473 from a previous 477.
Some 529,882 tests for COVID-19 were carried out in the past day, compared with a previous 490,711, the health ministry said.
March 17 (Reuters) - An AstraZeneca Plc (AZN.L) executive said the British drugmaker would consider not submitting its COVID-19 vaccine for approval in the United States if the regulatory process takes too long, the Financial Times reported on Thursday.
The company's research and development head, Mene Pangalos, said AstraZeneca would instead focus on selling the vaccine in other countries, though it will continue talks with the U.S. Food and Drug Administration, according to the report.
AstraZeneca did not immediately respond to a Reuters request for comment.
"We don't need to push it in places we are not needed or wanted," Pangalos told the Financial Times.
Giving up on U.S. approval would be a fresh setback for the vaccine which has had a tumultuous 18 months.
Last year, production problems forced the company to cut deliveries to the European Union, prompting the bloc to launch a legal challenge that has been settled.
Countries including Britain, Australia and Canada have also restricted its use among certain age groups following links to rare blood clots.
The shot has faced questions since late 2020, when the drugmaker and Oxford University published data from its first large-scale trial with two different efficacy readings as a result of a dosing error.
In March last year, U.S. health officials criticized the drugmaker for using "outdated information" to show how well its vaccine worked, a highly unusual public rebuke. read more
Days later, AstraZeneca published results showing diminished, though still strong, efficacy.
AstraZeneca Chief Executive Officer Pascal Soriot in July last year said it still planned to seek U.S. approval for its vaccine, authorized in some 170 countries, even though the process was taking longer than expected. read more.
3/17/22 “We believe Heterologous Boost makes sense for INO-4800 given our T Cell response, safety profile, thermostability, and the ability to readminister. We hope to have more news to share soon.
Thank you and I apologize for not being able to share additional news at this time
Investor Relations”
3/17/22 Alnylam seeks compensation from Moderna and Pfizer in suits over patented delivery of their Covid-19 vaccines
https://endpts.com/alnylam-seeks-compensation-from-moderna-and-pfizer-in-suits-over-patented-delivery-of-their-covid-19-vaccines/
RNAi therapeutics juggernaut Alnylam Pharmaceuticals on Thursday announced that it’s suing and seeking money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which have been integral to the way both companies’ mRNA vaccines work.
The suits, filed in the Delaware district court, both seek “fair compensation for use of its technology” but “no less than a reasonable royalty.” And if successful, the biotech will dip into two of the richest revenue streams the biopharma industry has ever seen.
The suits explain how Alnylam scientists more than a decade ago invented this new class of non-natural lipid nanoparticles, comprising a cationic (or positively charged) lipid with biodegradable groups that has proved critical for the Covid-19 vaccines and several marketed RNA therapies.
These so-called LNPs can protect the delicate RNA until it’s delivered to the cell, and then they’re metabolized and eliminated from the body.
In the case of Pfizer, the suit notes that every one of the company’s Covid-19 vaccines contains this infringing cationic lipid, known as ALC-0315.
How does Alynylam know that its patents have been infringed? The company explains how ALC-0315’s chemical name is ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), and the prescribing information for Pfizer’s Covid vaccine Comirnaty states that each dose contains that same chemical, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate).
For Moderna, although the company claims to have its own “proprietary lipid-nanoparticle-delivery system,” Alnylam said it “relies on the patented Alnylam LNP Technology” and that the “biodegradability of Moderna’s lipid system employs the patented Alnylam LNP Technology.”
The suit also explains how, prior to the pandemic, about a decade ago, Alnylam and Moderna began discussing a way for Moderna to license some of Alnylam’s IP.
In Feb. 2014, Moderna and Alnylam entered into a confidentiality agreement, allowing Alnylam to share secrets with top Moderna execs, including a “detailed PowerPoint disclosing Alnylam’s LNP Technology and how those LNPs could be used for developing RNA-based pharmaceuticals. Alnylam further disclosed valuable rodent and non-human primate pharmacology experiments that showed superior in vivo elimination of its biodegradable LNPs, while also showing superior potency,” the suit alleges.
A Moderna spokesperson told Endpoints News in a statement, “Alnylam has engaged in what can only be seen as blatant opportunism—improperly expanding the scope of a ten-year old patent in an attempt to stake a claim to unprecedented and meaningful innovations in the mRNA space.” The company also drew a line between the two companies’ RNA delivery vehicles:
Moderna’s LNPs do not resemble Alnylam’s work, and any assertion that the Alnylam patent covers Moderna’s COVID-19 vaccine is specious. Alnylam’s lipids were originally tailored for intravenous delivery of a different type of RNA, and Moderna discovered many years ago that such lipids were insufficient for delivering mRNA directly into the arm. Starting in 2014, Moderna designed new lipids that overcame this mRNA delivery challenge, and it is those novel lipids which are found in our LNPs.
Meanwhile, for years, Moderna has been battling a tiny Pennsylvania biotech known as Arbutus over patents for a technology required to deliver its mRNA drugs and vaccines, known as lipid nanoparticles or LNP. And Arbutus and another company recently sued Moderna for infringing on their patent on a lipid nanoparticle platform that they also said was crucial to the delivery of Moderna’s widely-used vaccine.
Alnylam is no stranger to lawsuits itself. The company tackled Dicerna in court, claiming the RNAi rival had essentially purloined some of its trade secrets by hiring a group of ex-Sirna scientists. Dicerna agreed to pay about $25 million in cash and stock to settle the litigation.
3/17 The study, which began last December at Chang Gung Memorial Hospital (CGMH), involved 340 participants, average age 35, who had already received two doses of the AstraZeneca COVID-19 vaccine, director Chiu Cheng-hsun said at a press conference.
The participants were divided into four groups and given a full dose of either the Pfizer-BioNTech (BNT), Taiwan's Medigen, or the Moderna vaccine, or a half-dose of Moderna, said Chiu, who also serves as vice superintendent of CGMH's Linkou branch.
The study, the first of its kind conducted in Taiwan, also examined the changes in the participants' T-cell immune responses, which play an important role in preventing severe COVID-19 symptoms, according to Chiu.
It found that T-cell responses in the full-dose Moderna recipients rose 4.2-fold, [4800 will shine in Advaccine’s heterologous booster trial in China], 3.9-fold with the Moderna half-dose, 3.3-fold with Medigen, and 3.1-fold with BNT, according to Chiu.
The study mixed not only vaccine brands but also technologies, as AstraZeneca is a viral vector vaccine, while Moderna and BNT are messenger RNA vaccines and Medigen is a protein subunit vaccine.
After 28 days, the study found that the participants who had received the Moderna booster - either as a full or half dose - had higher levels of neutralizing antibodies than those who had gotten the other two brands, Chiu said.
The neutralizing antibody levels had risen 47.7-fold among the full-dose Moderna recipients, 39.8-fold among those who had gotten a half-dose of Moderna, 32.2-fold among the BNT recipients, and 12.7-fold among those who had received the Medigen booster, he said.
In terms of neutralizing antibodies against the Omicron variant of the COVID-19 virus, the data showed an 86.6-fold rise in the full-dose Moderna group, an 81.5-fold rise in Moderna half-dose group, 71.1-fold among the BNT recipients, and 32.9-fold among those who had received the Medigen, Chiu said.
Neutralizing antibodies against the Delta variant, meanwhile, rose 97.8-fold in the full-dose Moderna group, 73.2-fold in the Moderna half-dose group, 57.8-fold in the BNT group, and 23.8-fold in the Medigen group, he added.
He said the side effects reported in the mix-and-match booster study were mild, with only 4.6 percent of the Medigen recipients and 30 percent of the Moderna group developing a fever.
Nearly all of the Moderna recipients experienced localized soreness of the arm, while 76 percent in the Medigen group had that side effect, Chiu added.
The results published Thursday reported findings that were valid only 28 days after the participants received the booster shots, which meant the study did not include data on the durability of the protection offered by the boosters.
Chiu said similar studies in other countries have shown that protection declines more slowly and less severely after a booster shot than after a second vaccine dose. The research team at CGMH will continue to collect data from the participants in the Taiwan study, he added.
As of Wednesday, 83.23 percent of the eligible population in Taiwan had received at least one shot of a COVID-19 vaccine, 77.73 percent had received at least two shots, while 47.16 percent of those eligible had gotten a booster, just shy of the government's goal of at least 50 percent, according to the Central Epidemic Command Center (CECC).
To date, Taiwan has authorized COVID-19 vaccines for people aged 12 and over and booster shots for those who are at least 18.
https://focustaiwan.tw/sci-tech/202203170015
we’re also evaluating the feasibility of an additional ex-U.S. heterologous boost trial for INO-4800 as a booster in a non-inferiority clinical trial, comparing -- compared to previously approved viral vector and inactivated COVID-19 vaccines. This will complement the ongoing booster trials that are being conducted in China by our partner Advaccine. Viral vector and inactivated COVID-19 vaccines have been the most widely administered vaccine types globally, particularly in low to middle income countries, accounting for more than half of all doses delivered worldwide.
Currently approved and authorized vaccines may not meet the global demand for boosters to address their waning protection, a need which some regulatory agencies are considering with respect to evaluating a clinical pathway for heterologous boost candidates and clinical trials.
In terms of additional heterologous boost, we’re deeply investigating the feasibility and execution ability of a heterologous boost trial, again outside the U.S. where we can compare with two other most prolifically utilized primary vaccine for COVID in viral vector and inactivated vaccines. So, we’re in the planning and feasibility stage. But, if this is a go, we think we can execute this all through 2022.
In addition to early data from independent studies that suggest a mix and match booster strategy of heterologous boosting may confer advantages over the homologous boosting approach, INO-4800’s key advantages as a DNA vaccine correspond well with desired features of a heterologous boost vaccine. These advantages include its observed T-cell immunity for disease protection, tolerability for re-administration, favorable thermostability profile for global transport, storage, and distribution and ease of construct design, line for timely scaling and manufacturing.
3/16/22 WHO delays review of Russia's Sputnik V vaccine on Ukraine conflict
https://www.reuters.com/business/healthcare-pharmaceuticals/who-delays-review-russias-sputnik-v-vaccine-ukraine-conflict-2022-03-16/
Kim's timeline at Oppenheimer was big. He is slowly but surely painting a masterpiece right now. Cellectra is ready for commercialization! HODL Inovians, this will not be plain sailing until we get to that day! All great things come with adversity and time.
3/15/22 data so far suggest that two doses of the J.&J. vaccine had an effectiveness of about 75 percent against hospitalization with the Omicron variant, comparable to the protection from the Pfizer-BioNTech vaccine. The researchers presented the findings last month at the Conference on Retroviruses and Opportunistic Infections in Denver.
in December, the C.D.C. recommended the mRNA vaccines over Johnson & Johnson’s for all adults, citing a risk of rare side effects like blood clots and Guillain-Barré syndrome. The agency found four cases of blood clots per million people who got the vaccine; women ages 30 to 39 had the highest incidence, at about 11 per million.
https://www.nytimes.com/2022/03/15/health/covid-johnson-vaccine.html
The mRNA vaccines, too, have been associated with uncommon side effects. They are thought to cause about 11 cases of myocarditis, or inflammation of the heart, for every 100,000 vaccinated males aged 16 to 29 years.
The mRNA vaccines, too, have been associated with uncommon side effects. They are thought to cause about 11 cases of myocarditis, or inflammation of the heart, for every 100,000 vaccinated males aged 16 to 29 years.
More data on different combinations of vaccines may clarify which is the safest and most effective in the long term, Dr. Dean said. The arrival of new variants may also give some vaccines an edge over others, she said.
In Africa, for example, distribution of a single-dose vaccine that can be refrigerated for months is by far the most practical option.
Johnson & Johnson has at least temporarily shut down the only plant making usable batches of the vaccine. But the South Africa-based Aspen Pharmacare is gearing up to supply large quantities to the rest of the continent. Only about 13 percent of Africans are fully vaccinated, and only about 1 percent have received a booster dose.
3/17/22 S. Korea's new COVID-19 cases spike to over 600,000 amid omicron spread
http://www.koreaherald.com/view.php?ud=20220317000208
South Korea's new daily COVID-19 cases spiked to more than 600,000 on Thursday, setting another record high, fueled by the spread of the highly transmissible omicron variant amid an easing of virus curbs.
The country reported 621,328 new COVID-19 infections, including 62 cases from overseas, raising the total to 8,250,592, the Korea Disease Control and Prevention Agency (KDCA) said.
The latest tally marks a 55 percent surge in just one day. South Korea has seen a spike in the caseload since it reported the first five-digit figures in late January of this year. Since then, the numbers have grown fast, surpassing 300,000 on March 9.
The death toll from COVID-19 more than doubled to a record high of 429, putting the total at 11,481. The fatality rate stood at 0.14 percent.
The number of critically ill patients, seen as a key indicator in the pandemic response, came to 1,159, down from 1,244 the previous day.
South Korea has been taking steps to ease virus restrictions to regain normalcy despite the virus surge, due largely to the pressure from small businesses and self-employed people hit hard by the pandemic.
The government is expected to announce Friday whether it will maintain the current social distancing or further relax the measures. Currently, an 11 p.m. business curfew and six-person cap on private gatherings are in place.
Health authorities believe the omicron wave is heading for its peak. Prime Minister Kim Boo-kyum has asked health officials to consider adjusting the classification for COVID-19 to a less dangerous type.
Seoul reported 128,375 cases, with the surrounding Gyeonggi Province registering 181,983 and the western port city of Incheon at 32,964.
As of Thursday, 32.21 million people out of the 52 million population, or 62.8 percent, had received booster shots. Fully vaccinated people came to 44.44 million, representing 86.6 percent, the KDCA said.
3/16/22 NEJM: Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron
https://www.nejm.org/doi/full/10.1056/NEJMc2202542
within the wide confidence intervals of our estimates, vaccine efficacy against symptomatic disease was 65% at most.
Our data provide evidence that a 4th dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease). A comparison of the initial response to the 4th dose with the peak response to a third dose did not show substantial differences in humoral response or in levels of omicron-specific neutralizing antibodies. Along with previous data showing the superiority of a 3rd dose to a 2nd dose, our results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a 4th dose. Furthermore, we observed low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious.
In this open-label, nonrandomized clinical study, we assessed the immunogenicity and safety of a fourth dose of either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) administered 4 months after the third dose in a series of three BNT162b2 doses (ClinicalTrials.gov numbers, NCT05231005. opens in new tab and NCT05230953. opens in new tab; the protocol is available with the full text of this letter at NEJM.org). Of the 1050 eligible health care workers enrolled in the Sheba HCW COVID-19 Cohort,1,2 154 received the fourth dose of BNT162b2 and, 1 week later, 120 received mRNA-1273. For each participant, two age-matched controls were selected from the remaining eligible participants
3/16/22 A covid surge in Western Europe has U.S. bracing for another wave
A surge in coronavirus infections in Western Europe has experts and health authorities on alert for another wave of the pandemic in the United States, even as most of the country has done away with restrictions after a sharp decline in cases.
Infectious-disease experts are closely watching the subvariant of omicron known as BA.2, which appears to be more transmissible than the original strain, BA.1, and is fueling the outbreak overseas.
Germany, a nation of 83 million people, saw more than 250,000 new cases and 249 deaths Friday, when Health Minister Karl Lauterbach called the nation’s situation “critical.” The country is allowing most coronavirus restrictions to end Sunday, despite the increase. The United Kingdom had a seven-day average of 65,894 cases and 79 deaths as of Sunday, according to the Johns Hopkins University Coronavirus Research Center. The Netherlands, home to fewer than 18 million people, was averaging more than 60,000 cases the same day.
In all, about a dozen nations are seeing spikes in coronavirus infections caused by BA.2, a cousin of the BA.1 form of the virus that tore through the United States over the past three months.
In the past two years, a widespread outbreak like the one now being seen in Europe has been followed by a similar surge in the United States some weeks later. Many, but not all, experts interviewed for this story predicted that is likely to happen. China and Hong Kong, on the other hand, are experiencing rapid and severe outbreaks, but the strict “zero covid” policies they have enforced make them less similar to the United States than Western Europe.
China posted a steep jump in daily coronavirus infections on March 15 with new cases more than doubling from a day earlier to a two-year high.
A number of variables — including relaxed precautions against viral transmission, vaccination rates, the availability of antiviral medications and natural immunity acquired by previous infection — may affect the course of any surge in the United States, experts said.
Most importantly, it is unclear at this point how many people will become severely ill, stressing hospitals and the health-care system as BA.1 did.
Another surge also may test the public’s appetite for returning to widespread mask-wearing, mandates and other measures that many have eagerly abandoned as the latest surge fades and spring approaches, experts said.
“It’s picking up steam. It’s across at least 12 countries … from Finland to Greece,” said Eric Topol, director of the Scripps Research Translational Institute in San Diego, who recently posted charts of the outbreak on Twitter. “There’s no question there’s a significant wave there.”
Topol noted that hospitalizations for covid-19, the disease caused by the virus, are rising in some places as well, despite the superior vaccination rates of many Western European countries.
At a briefing Monday, White House press secretary Jen Psaki said about 35,000 cases of BA.2 have been reported in the United States to date. But she offered confidence that “the tools we have — including mRNA vaccines, therapeutics and tests — are all effective tools against the virus. And we know because it’s been in the country.”
Kristen Nordlund, a spokeswoman for the Centers for Disease Control and Prevention, said in an email Tuesday that “although the BA.2 variant has increased in the United States over the past several weeks, it is not the dominant variant, and we are not seeing an increase in the severity of disease.” CDC data shows that, as of last week, BA.2 accounted for 23.1% of all new coronavirus infections in the United States, the largest percentage yet — up from 13.7% the week before. But BA.2 accounted for more than 38 percent of cases last week in parts of the Northeast and New England.
The seven-day average of cases in the United States fell 17.9 percent in the past week, according to data tracked by The Washington Post, while the number of deaths dropped 17.2 percent and hospitalizations declined 23.2 percent.
Predicting the future course of the virus has proved difficult throughout the pandemic, and the current circumstances in Europe elicited a range of opinions from people who have closely tracked the pathogen and the disease it causes.
In the United States, just 65.3 percent of the population, 216.8 million people, are fully vaccinated, and only 96.1 million have received a booster shot, according to data tracked by The Post. In Germany, nearly 76 percent are fully vaccinated, according to the Johns Hopkins data, and the United Kingdom has fully vaccinated 73.6 percent.
That lower vaccination rate is very likely to matter as BA.2 spreads further in the United States, especially in regions where it is significantly lower than the national rate, several experts said. And even for people who are fully vaccinated and have received a booster shot, research data is showing that immunity to the virus fades over time. Vaccine-makers Pfizer and BioNTech asked the Food and Drug Administration on Tuesday for emergency authorization to offer a fourth shot to people 65 and older.
“Any place you have relatively lower vaccination rates, especially among the elderly, is where you’re going to see a bump in hospitalizations and deaths from this,” said Céline Gounder, an infectious-diseases physician and editor at large for public health at Kaiser Health News.
Similarly, as the public sheds masks — every state has dropped its mask mandate or announced plans to do so — another layer of protection is disappearing, several people tracking the situation said.
“Why wouldn’t it come here? Are we vaccinated enough? I don’t know,” said Kimberly Prather, a professor of atmospheric chemistry and an expert on aerosol transmission at the University of California at San Diego.
“So I’m wearing my mask still. … I am the only person indoors, and people look at me funny, and I don’t care.”
Yet BA.2 appears to be spreading more slowly in the United States than it has overseas, for reasons that aren’t entirely clear, Debbie Dowell, chief medical officer for the CDC’s covid-19 response, said in a briefing Saturday for clinicians sponsored by the Infectious Diseases Society of America.
How Hong Kong's 'zero covid' policy backfired
“The speculation I’ve seen is that it may extend the curve going down, case rates from omicron, but is unlikely to cause another surge that we saw initially with omicron,” Dowell said.
One reason for that may be the immunity that millions of people acquired recently when they were infected with the BA.1 variant, which generally caused less-severe illness than previous variants. Yet no one really knows whether infection with BA.1 offers protection from BA.2.
“That’s the question,” said Jeffrey Shaman, an epidemiologist at the Columbia University Mailman School of Public Health. “Better yet, how long does it provide protection?”
Topol said the United States needs to improve its vaccination and booster rates immediately to protect more of the population against any coming surge.
“We have got to get the United States protected better. We have an abundance of these shots. We have to get them into people,” he said.
Biden administration officials said that whatever the further spread of BA.2 brings to the United States, the next critical step is to provide the $15.6 billion in emergency funding that Congress stripped from a deal to fund the government last week.
That money was slated to pay for coronavirus tests, more vaccines and antiviral medications.
“That means that some programs, if we don’t get funding, could abruptly end or need to be pared back, Psaki said at Monday’s briefing. “And that could impact how we are able to respond to any variant.”
A rise in BA.2's prevalence could be a boon for those scrambling for courses of Evusheld, an antibody drug manufactured by AstraZeneca to protect immunocompromised Americans. While BA.2 appears to retain "near-full susceptibility" to Evusheld, the Food and Drug Administration recently warned that doses would need to be doubled to protect against BA.1. AZD7442 sold under the brand name Evusheld is a combination of two human monoclonal antibodies, tixagevimab and cilgavimab targeted against the surface spike protein of CV. It is dMAb® cloned by $37.6M grant from DARPA .
? 2H22: Initiate COVID-19 dMAb trial
https://www.cbsnews.com/news/covid-cases-ba2-omicron-sub-variant-cdc/
However, a surge in BA.2 cases could sideline sotrovimab, a monoclonal antibody drug produced by GlaxoSmithKline and Vir Biotechnology. Early laboratory studies suggest BA.2 could significantly reduce the effectiveness of the treatment.
- DARPA to fund innovative public-private partnership between INOVIO, The Wistar Institute, AstraZeneca, the University of Pennsylvania and Indiana University
- $37.6 million grant from DARPA will leverage AstraZeneca's monoclonal antibody and INOVIO's DNA-encoded monoclonal antibody (dMAb®) technologies in the fight against COVID-19
- 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
Recombinant monoclonal antibodies, which represent the largest segment of pharmaceutical markets today with more than $100 billion in sales, are designed to enhance the immune system's ability to regulate cell functions. However, the technology has some limitations, including long and costly laboratory development and large-scale production, limited duration of in vivo potency, and a pharmacokinetic profile that can result in toxicity. INOVIO's dMAb technology offers a disruptive and differentiated solution to the challenges and limitations associated with conventional recombinant monoclonal antibody-based treatments. The company can encode the DNA sequence for a specific monoclonal antibody in a DNA plasmid and deliver the plasmid directly into cells of the body using the company's proprietary smart device called CELLECTRA®. This specific DNA medicine serves as a genetic blueprint that instruct the patient's body to build its own highly specific antibodies in vivo.
https://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-to-Develop-DNA-encoded-Monoclonal-Antibody-dMAb-Candidates-to-Treat-COVID-19-with-Funding-from-the-Defense-Advanced-Research-Projects-Agency-DARPA-and-the-Department-of-Defenses-DoD-Joint-Program-Executive-Office-for-Chemical-Biological-Radiol/default.aspx
Ino ended 4Q21 with $401.3M in cash, cash equivalents and short term investments. As of December 31, 2021, Inovio had 217.4M common shares outstanding. 401.3/217.4=$1.85/sh cash
Wall st gave only $3.1-1.85=$1.25/sh to VGX-3100 and zero to CV vaccine and the rest of pipeline. So any good news on 4800 and VGX-3100 would be huge upside.
INO-4800
? April 2022: Advaccine heterologous and homologous boost P2 trials Interim Readouts. Apply for EUA. WHO STV Interim Readout. Grant EUL quickly as WHO owns data. COVAX pre-orders 4800 and C2K
? May 2022: Order from China and LMICs for pGx9501 booster, C2K Device. Ino earns some regulatory, commercialization $206M milestones. Royalty equals a high single-digit percentage of annual net sales. Grease the skid for HK IPO w/ good valuation
? 4Q22: INNOVATE Interim Readout. Primary Endpoint: Severe Disease. Apply for EUAs in Philippines ????, Colombia ????, Brazil ????, Mexico ????
VGX-3100
? 4Q22: Report REVEAL2 efficacy data and safety follow-up through week 40. QIAGEN biomarker final selection
? 2H22: Apollo Bio Interim Readout. Ino earns some $20M milestone
INO-3107
? 3Q22: P1/2 immune responses and early clinical benefit data. Apply for Breakthrough Therapy Designation, eligible for PRVs.
? 4Q22: Start P3, fast tracked as ODD
INO-5401
? 2Q22: Present additional overall survival OS36 data including median OS for MGMT-methylated cohort
Platform Development
? 1H22: Report INO-4500 Lassa P1b data
? 2H22: Report INO-4201 Ebola P1b booster data
? 2H22: Initiate COVID-19 dMAb trial
? 2H22: Report INO-4700 MERS P2 data
? October 2022: A Phase 1 Study of INO-A002 dMAb™ in Healthy Dengue Virus-naive Adults.
Apply for Fast Track Designation
https://clinicaltrials.gov/ct2/history/NCT03831503?A=9&B=10&C=merged#StudyPageTop
Overall Status: Active, not recruiting
Last Update Posted : 10/19/21
Enrollment: 30 [Actual]
Primary Completion, Study Completion: October 2022 [Anticipated]
? 4Q22 MedImmune is currently conducting a P2 clinical trial of MEDI0457 in patients with head and neck squamous cell carcinomas (HNSCC). MedImmune has completed the final data cut off for the trial and plans to complete the clinical study report by the end of 2022. The Company expects that MedImmune will continue to sponsor this study until study termination. MedImmune will also continue providing financial support for an externally sponsored research study of MEDI0457 with The University of Texas MD Anderson Cancer Center until study completion.
https://clinicaltrials.gov/ct2/history/NCT03439085?A=13&B=14&C=merged#StudyPageTop
The deal, originally signed in 2015, was worth $27.5 million upfront with $700 million in biobucks down the line. Inovio has managed to pick up a couple million dollars through the partnership, but the remaining funds are now off the table.
Ino reacquires the rights to INO-3112, could license out again for large deal.
? INO-5151 (INO-5150 + INO-9012) for the Treatment of Prostate Cancer
We are developing INO-5151, which consists of DNA plasmids targeting Prostate Specific Antigen (PSA) and Prostate Specific Membrane Antigen (PSMA), combined with INO-9112, the IL-12 plasmid, for the treatment of prostate cancer. In the United States in 2022, there will be an estimated 268,490 new cases of prostate cancer and about 34,500 deaths due to this cancer.
https://clinicaltrials.gov/ct2/show/NCT03835533?term=INO-5151&draw=2&rank=1
Estimated Primary Completion Date :
March 2022
Estimated Study Completion Date :
March 2023
In 2019, we announced a clinical collaboration with Parker Institute for Cancer Immunotherapy (PICI) and the Cancer Research Institute (CRI) as part of which INO-5151 is being combined with an immune modulator (CDX-301, FLT3 ligand, a dendritic cell mobilizer) and a PD-1 immune checkpoint inhibitor (nivolumab) in participants with metastatic castration-resistant prostate cancer (mCRPC), in a PICI-sponsored platform trial (PORTER). This combination trial is an open-label, non- randomized, exploratory platform trial designed to assess the safety and antitumor activity of multiple immunotherapy-based combinations in participants with mCRPC who have received prior secondary androgen inhibition. This trial will evaluate biomarkers of immune activity and clinical outcomes using a multi-omic, multi- parameter approach. Our immunotherapy is one arm of this PICI-supported trial, and recruitment is ongoing. Under the agreement, PICI will design and conduct the clinical trial, working in collaboration with its established network of clinical academic and industry cancer centers, with funding support from CRI. We will provide financial contributions based on the actual costs of the trial, if INO-5151 reaches the initiation of a Phase 3 trial.
12/14/21: The first participant has been dosed in the P3 trial of VGX-3100 for cervical HSIL in China. This trial is being run by ApolloBio and is similar in design to REVEAL2. The trial is expected to enroll up to 84 participants.
In addition to the upfront payment that we received in 2018, we are entitled to receive up to an aggregate of $20M upon the achievement of specified milestones related to the regulatory approval of VGX-3100. We will be entitled to receive royalty payments based on a tiered percentage of annual net sales, with such percentage being in the low- to mid-teens.
• Booster market is much larger than primary vaccine market
• Inactivated and viral vector vaccines have been administered primarily in Low- and Middle- Income countries
• About 2.4 billion doses of the Chinese vaccines have been administered in China, but almost 1 billion doses have gone to 110 other countries
• Global demand for heterologous boosters cannot be met with currently licensed (EUA or full authorization) for primary series or those not currently licensed but with Phase 3 data efficacy data
3/15/22 China Covid cases hit two-year high with millions in lockdown as outbreak spreads
Nearly 90% of new infections in Jilin province, while tens of millions of people across the country remain confined to their homes
https://www.theguardian.com/world/2022/mar/15/china-covid-cases-hit-two-year-high-with-millions-in-lockdown-as-outbreak-spreads
China has posted a steep jump in daily Covid-19 infections with new cases more than doubling from a day earlier to a two-year high as a virus outbreak expanded rapidly in the north-east.
A total of 3,507 domestically transmitted cases with confirmed symptoms were reported on Monday across more than a dozen provinces and municipalities, the National Health Commission said, up from 1,337 a day earlier.
Since the coronavirus first emerged in the central city of Wuhan in late 2019, China had successfully suppressed large-scale outbreaks through its strict “zero-Covid” strategy, which involved hard lockdowns that confined huge sections of the population to their homes.
While the country’s case load is still tiny by global standards, health experts said the rate of increase in daily cases over the next few weeks would be a crucial factor in determining whether its tough containment approach was still effective against the rapidly spreading Omicron variant.
A Covid-19 forecasting system run by Lanzhou University in China’s nort-west predicted that the current round of infections would eventually be brought under control in early April after an accumulated total of about 35,000 cases.
The university said in its latest assessment published on Monday that while the outbreak was the most serious on the mainland since Wuhan in 2020, China could bring it under control as long as stringent curbs remained in place.
At least 11 cities and counties nationwide have been locked down because of the latest surge, including the southern tech hub of Shenzhen, home to 17 million people.
In the financial hub of Shanghai, authorities battling an outbreak across the city were cordoning off individual apartment buildings and testing all residents.
China’s aviation regulator said that 106 international flights scheduled to arrive in Shanghai would be diverted to other domestic cities from 21 March to 1 May due to Covid.
Confirmed symptomatic infections in Shanghai stood at 21 on Monday, including 12 imported from overseas, with an additional 130 asymptomatic cases.
Nearly 90% of the mainland’s confirmed new symptomatic cases on Monday were found in the north-eastern province of Jilin, which has banned its 24.1 million population from travelling in and out of the province and across different areas within the province without notifying local police.
Jilin officials should step up the preparation of temporary hospitals and designated hospitals and make use of idle venues to ensure all infections and their close contacts were isolated, a local Communist party authority-backed paper said, citing the provincial head of the party.
An outbreak at Volkswagen Group factories in the Jilin city of Changchun also prompted three sites to shut on Monday for at least three days, according to a spokesman.
‘It’s like we are being left to die’: Hong Kong tackles deadliest Covid wave
The number of new asymptomatic cases, which China does not classify as confirmed cases, stood at 1,768 compared with 906 a day earlier. There were no new deaths, leaving the death toll unchanged at 4,636.
As of 14 March, mainland China had reported 120,504 cases with confirmed symptoms, including both local ones and those arriving from outside the mainland.
So what are the next steps in our fight against COVID?
A fourth dose, boosters for younger kids, masks, and keeping the virus at bay
https://mb.com.ph/2022/03/15/so-what-are-the-next-steps-in-our-fight-against-covid/
South Korea is showing over 300,000 cases a day at the time of this writing. Vietnam and Germany remain at over 100,000 daily cases. In Southeast Asia, the Philippines is showing the lowest case numbers per million population. Vietnam has surpassed all countries except Indonesia in total case numbers, and Malaysia recently surpassed our pandemic total. This is proof that Omicron is still very much around, and we need both vaccination and masks to defeat it.
'Ample room for uncertainty': As COVID-19 cases rise again in Europe, could US see the same?
The possibility of a new variant or a spike in cases always exists given the nature of viruses, said Ogbonnaya Omenka, an assistant professor and director of diversity at the Butler University College of Pharmacy and Health Science.
"A wave in Europe and other countries for that matter, might occur in the United States as well," Omenka told USA TODAY. "Because it is an infectious disease, unless we eradicate it, there is bound to be that possibility of its return ... As the virus variants have shown, even the possible return is not predictable in terms of its severity or degree of similarity to the previous forms."
Another factor at play in the rise of cases and a possible next wave: human behavior surrounding virus prevention measures. Omenka said human activities are among the factors that "can influence how things unfold."
England, Spain and France are among European countries that recently announced a shift in pandemic strategy: treating the virus as a part of daily life without full shutdowns.
In England, Prime Minister Boris Johnson announced the end of all domestic COVID-19 restrictions at the end of last month, including lifting the legal requirement to self-isolate after testing positive.
"An 'endemic approach' indicates focus on living with the virus rather than eradicating it. As a result of the relaxation of certain guidelines, it is left for individuals to decide whether to continue measures such as mask-wearing or not," Omenka said. "It is not unusual for the public to start lowering the levels of their perceived risk of a threat, after dealing with it for an extended time."
The possible European surge also comes alongside conflict in Ukraine after the Russian invasion, leading to rising concerns about a public health crisis in the region sparked by densely crowded shelters and forced travel across borders. The WHO said earlier this month that the conflict may cause a surge in infections, straining scarce resources and contributing to more suffering and death.
Europe isn't the only part of the world seeing a spike in COVID-19 cases. China ordered a lockdown of the residents of the city of Changchun, closed schools in Shanghai and urged the public not to leave Beijing this weekend amid a new spike in cases in the area likely from omicron.
In the United States, cases are still trending downward following the initial wave of omicron: an average of 34,805 new daily cases, the lowest case rate since July, according to CDC data.
But only 44.3% of the U.S. population has received a booster dose, despite CDC data showing booster shots of the Pfizer-BioNTech and Moderna vaccines have proven highly effective at preventing omicron-related hospitalizations. Just this weekend, former President Barack Obama tested positive for the virus after experiencing some symptoms for a "couple days." He is fully vaccinated and boosted.
"At this point, a new wave COVID-19 anywhere ought to be viewed as a potential new wave worldwide," Omenka said. "This is a more beneficial approach regardless of the outcome."
On a global level, the World Health Organization recently reversed its stance on booster shots and now "strongly supports urgent and broad access" to booster doses after previously insisting that boosters weren't necessary and contributed to vaccine inequity.
BA.2, known as the "stealth" omicron variant, is making up a growing number of cases in some countries, and some studies show that it may be up to 30% more transmissible than the original omicron variant. Cases of BA.2 made up an estimated 11.6% percent of cases in the United States as of March 5, according to CDC data, up from 6.6% Feb. 26.
While viruses always mutate, there's a higher threat for populations when COVID-19 is active and able to spread in communities, according to Omenka.
"The common expectation is that new variants will keep arising from the virus," he said. "Since the relationship is like an arms race, we are left with modifying our approaches according to best available evidence. So, the forecast is made with ample room for uncertainty."
3/14/22 Dr. Gottlieb says China is 'very vulnerable' to omicron subvariant spread despite 'zero-Covid policy'
Low levels of immunity are complicating China's efforts to limit spread during its surge in cases of the new Covid omicron BA.2 subvariant, Dr. Scott Gottlieb told CNBC on Monday.
"China has a population that's very vulnerable to this new variant. This is a much more contagious variant, it's going to be harder to control, and they don't have a population that has natural immunity," Gottlieb said.
The increasing number of cases of BA.2, known as "stealth" omicron, in mainland China have led some major cities to shutter nonessential businesses and move to online schooling.
Low levels of natural immunity are complicating China's efforts to limit spread during its recent surge in cases of the new Covid omicron BA.2 subvariant, Dr. Scott Gottlieb told CNBC on Monday.
"China has a population that's very vulnerable to this new variant. This is a much more contagious variant, it's going to be harder to control, and they don't have a population that has natural immunity," the former Food and Drug Administration commissioner said in an interview on "Squawk Box."
The BA.2 omicron subvariant, colloquially called "stealth" omicron, was first identified in late 2021.
"They haven't deployed vaccines that are very effective against this particular variant, this omicron variant, and so they're very vulnerable to spread right now. They didn't use the time that they bought themselves to really put in place measures that would prevent omicron from spreading," said Gottlieb, who is on the board of Covid vaccine maker Pfizer.
The increasing number of BA.2 cases in mainland China has led some major cities on Monday to shutter nonessential businesses and move schools to online instruction. The outbreak is the mainland's worst since the height of the pandemic in 2020, and the strict response to it indicates a continuation of China's zero-Covid strategy.
China's zero-Covid policy entails strict quarantines and travel restrictions both domestic and international. While the policy has successfully kept cases down since the height of the pandemic, health officials have warned that China's resulting lack of exposure to Covid leaves it vulnerable to harder-to-control strains such as omicron.
The latest omicron outbreak in China also has economic repercussions, since it could hinder already struggling supply chains, particularly for tech companies.
Apple shares dropped more than 2% midday, as the Chinese city of Shenzhen's health orders halted activity at production plants of Foxconn, an important supplier to the iPhone maker. Activity will resume once Foxconn receives government approval to do so, the company told CNBC.
Gottlieb said China's outbreak could be bigger than what is being reported, adding uncertainty to the situation.
"We really don't know how large the outbreak is in China right now," Gottlieb said. "We don't know if there's tens of thousands of cases or hundreds of thousands of cases."
Mainland China reported 1,437 new confirmed cases as of Sunday for a total of 8,531 domestically transmitted active cases.
"People are going to get infected in those homes where they're confining people right now, and the big question is: How much infection do they have and how long will this last?" Gottlieb said.
Finished dosing 1/27/22. I have said Advaccine finished 267-ppl Heterologous Booster 4800 w/ Sinovac trial before Lunar NewYear 2/1/22. China normally shuts down 2 weeks for celebration. So, Advaccine wasted no time. They are motivated to expedite the trials for IPO and get high valuation to fund global commercialization. Expect Interim Readout April 2022 for 2,4,6,8 wks After dosing.
Updated: 3/9/22
Recruiting time: From2021-12-22 To 2022-01-27
http://www.chictr.org.cn/showproj.aspx?proj=131321&fbclid=IwAR1AVdMvFu74Nx8-pOSgRo4VjZMy7l0knDclViZlyOK_rPbfPJwTi2OfN64
1. Main purpose: To evaluate the humoral immune response of booster immunization against new crown DNA in healthy subjects aged 18 and over who have received 2 doses of inactivated new crown vaccine; The safety of boosting the immunization of the new crown DNA in the above healthy subjects; 2. Secondary purpose: To evaluate the cellular immune response of boosting immunization against 2019-nCoV DNA in healthy subjects aged 18 and above who have completed 2 doses of 2-dose inactivated SARS-CoV-2 vaccine; 3. Exploratory purpose: To evaluate the durability of immune response to booster immunization against new crown DNA in healthy subjects aged 18 and over who have completed 2 doses of inactivated new crown vaccine; Neutralization of Covid-19 DNA by booster immunization against SARS-CoV-2 variants in healthy subjects aged one year and older.
Inclusion Criteria:
3. For subjects in group A, complete two doses of the approved inactivated new crown vaccine within 3 months (± 15 days) before participating in the screening of this study, and the interval between the second dose and the first dose The time is 21 days (+10 days);
4. For subjects in group B, two doses of the approved inactivated COVID-19 vaccine should be completed within 6 months (± 15 days) before participating in the screening of this study, and the interval between the second dose and the first dose should be The time is 21 days (+10 days);
3/14/22 Vaccine maker stocks rise as China battles worst Covid outbreak since 2020
Shares of Moderna, BioNTech, Pfizer and Johnson & Johnson rose on Monday as China battles its worst Covid outbreak in two years.
Jefferies' analysts, in a note on Monday, said the outbreak and lockdowns in China have fueled fear among investors that the pandemic will take longer to resolve than expected.
"Vaccine makers will continue to trade on global fear of more waves," Michael Yee, an equity analyst, wrote in the Monday note.
https://www.cnbc.com/2022/03/14/vaccine-maker-stocks-rise-as-china-battles-worst-covid-outbreak-since-2020.html
[This bodes well for Ino as dvaccine heterologous and homologous boost P2 trials Interim Readouts April 2022. Apply for EUA. WHO STV Interim Readout. Apply for EUL. COVAX Pre-orders.
Expect JK and Hartaj Singh to expound China pandemic in a fireside chat and 1x1 investor meetings at Oppenheimer's 32nd Annual Healthcare Conference on 3/15/22.
INOVIO is evaluating the feasibility of an additional ex-US heterologous boost (vaccination with a different vaccine from the primary series) trial with INO-4800 as a booster in a non-inferiority clinical trial compared to viral vector and inactivated COVID-19 vaccines.
Currently licensed vaccines may not meet the global demand for boosters to address waning protection from these primary vaccinations, a need which some regulatory agencies are considering with respect to evaluating clinical pathways for heterologous boost vaccines.
Key features of INOVIO's DNA vaccine technology that make it a potentially favorable primary and booster candidate include generating T-cell responses against multiple variants of concern, lack of anti-vector immunity, tolerability of re-administration, and thermostability for transport, storage, and distribution.]
Shares of the major vaccine makers rose on Monday as China battles its worst Covid outbreak since 2020, fueling fear that the pandemic will drag on which could drive demand for future vaccine orders.
Moderna's stock jumped more than 8% to close at $150.07. In the morning, the biotech company's stock had surged nearly 20% to hit an intraday high of $166.75.
BioNTech soared 12% to close at $151.92, Pfizer jumped 4% to $52.25, and Johnson & Johnson rose more than 1% to $171.69. Novavax turned negative and closed down more than 1% at $71.93, after jumping nearly 15% in the morning to hit an intraday high of $83.25.
The vaccine makers' stocks rose even as the broader market fell, with traders monitoring the impact of the war in Ukraine and anticipating a rate hike by the Federal Reserve this week.
Major cities in China have placed fresh restrictions on business activity to fight the outbreak, driven by the omicron Covid variant. Shenzhen, a major tech hub in southern China, has told companies to halt all non-essential business activity or have employees work from home, while Changchun in the northeast has entered a lockdown. Apple supplier Foxconn has halted production in Shenzhen, while Toyota and Volkswagen have suspended production in Changchun.
In Shanghai, China's financial hub, schools have gone back to online classes and officials told residents not to leave the city unless absolutely necessary. China has a strict zero-Covid strategy that uses tough measures to quickly stamp out outbreaks.
Mainland China reported more than 1,400 new Covid infections as of Sunday for a total of over 8,500 domestically transmitted cases, according to China's National Health Commission. While low by international standards, it's the most in China since March of 2020. China has not reported any new Covid deaths.
Jefferies' analysts, in a note on Monday, said the outbreak and lockdowns in China have fueled fear among investors that the pandemic will take longer to resolve than expected.
"Vaccine makers will continue to trade on global fear of more waves," Michael Yee, an equity analyst, wrote in the Monday note.
While China will likely continue to rely on its domestic vaccine Sinopharm, the outbreak will keep the world on alert and probably drive demand for Moderna's vaccine on the margins, according the Jefferies' note. Moderna is projecting at least $19 billion in vaccine sales for 2022, while Pfizer is projecting $32 billion in revenue for its shots.
In the U.S., Covid infections continue to decline after an unprecedented surge of infection driven by the omicron variant in December and January. The U.S. reported an average of more than 35,000 new Covid cases on Sunday, a 24% drop from the week prior, according to a CNBC analysis of data from Johns Hopkins University. New Covid cases in the U.S. peaked at an average of more than 800,000 cases a day on Jan. 15. However, more than 1,200 people are still dying every day on average from Covid in the U.S., though that's down 9% from the week prior, according to the data.
The Centers for Disease Control and Prevention said last week that 98% of people in the U.S. now live in areas where they no longer need to wear facemasks in indoor public places.
"For the Omicron variant strain, the neutralizing antibody concentration of 3 doses of high-end (Medigen) vaccines was completed. Compared with the neutralization data of the Wuhan prototype strain, the decrease in the neutralizing antibody against Omicron was similar to that of the existing three-dose mRNA vaccine.
The serum of the vaccine can still neutralize Omicron, indicating that the third dose of the high-end vaccine is expected to provide a considerable degree of protection to Omicron.“
https://www.precisionvaccinations.com/vaccines/medigen-covid-19-vaccine
https://www-medigenvac-com.translate.goog/news_view.php?id=169&_x_tr_sl=zh-CN&_x_tr_tl=en&_x_tr_hl=en
2022/01/24
High-end third dose booster, which can effectively boost antibodies against Omicron
Research data on the high-end third-injection supplement shows that regardless of whether the first two doses of high-end or AZ vaccine are administered, the third-injection high-end can increase the concentration of neutralizing antibodies, thereby enhancing the protection against highly concerned variant strains (VOC). In the test of 3 doses of high-end vaccine, the neutralizing ability of the subjects' serum to Omicron was greatly improved; in the test of 2 doses of AZ vaccine plus the third dose of high-end vaccine, the neutralizing antibody concentration of subjects also increased by 5.7 times . Considering the safety tolerance and excellent immune generation of the protein subunit vaccine, different vaccine platforms (such as adenovirus vaccine, mRNA vaccine) will be mixed with the supplementary dose of the third subunit protein vaccine.
For the Omicron variant strain, the neutralizing antibody concentration of 3 doses of high-end vaccines was completed. Compared with the neutralization data of the Wuhan prototype strain, the decrease in the neutralizing antibody against Omicron was similar to that of the existing three-dose mRNA vaccine. Most people tested The serum of the vaccine can still neutralize Omicron, indicating that the third dose of the high-end vaccine is expected to provide a considerable degree of protection to Omicron.
On 1/18, Buli Taoyuan Hospital published the data of 2 doses of AZ, mixed with the third dose of high-end supplemental doses in the international database medRxiv, showing that mixed use of the third dose of high-end vaccines can improve the level of the Wuhan prototype strain and the Omicron variant respectively. and antibody titers. Serum samples given only two doses of AZ vaccine showed poor neutralization capacity for Omicron. One month after the high-end injection of the third injection, blood was drawn, and it was found that the neutralizing antibody titer against the Omicron variant was much higher than the antibody value on the base day of the injection, an increase of 5.7 times. It can be seen that the combination of 2 needles of AZ and the third needle of high-end will help to improve the immunity of individuals to neutralize the Omicron variant.
In addition, the high-end vaccine has also jointly implemented the third-injection mixed trial of "Mix and Match" with the international organization CEPI. The first two doses of AZ, Modena or high-end vaccine will be evaluated, and the above three vaccines will be used as the third booster. safety and immunogenicity. The trial will be carried out in four clinical trial centers including National Taiwan University Hospital, Taipei Rong General Hospital, Wanfang Hospital and the Affiliated Hospital of Gaoyi Medical University. This data will help evaluate the immune effects of mRNA vaccines, adenovirus vaccines and high-end vaccines.
3/13/22 Focus on drug targets: From diagnosis to treatment, the latest research progress of Prostate-specific membrane antigen (PSMA). Tumor vaccine:
INO-5401 is a DNA vaccine targeting hTERT, WT1 and PSMA developed by Inovio Pharmaceuticals, and may be combined with checkpoint inhibitors to become a powerful cancer immunotherapy. The National Cancer Institute previously emphasized the role of hTERT, WT1 and PSMA. According to reports, these three antigens are overexpressed and frequently mutated in a variety of human cancers. Targeting these antigens in the treatment of cancer patients has proven effective of. At the 2020 annual meeting of the Society of Neuro-Oncology (SNO), data from a phase 1/2, open-label, multi-center trial conducted in 52 patients with glioblastoma (GBM) was announced. Studies have shown that the combination of INO-5401 + INO-9012 with Libtayo, radiotherapy (RT) and temozolomide (TMZ) is tolerable and immunogenic, and may improve the median survival of newly diagnosed GBM patients. Inovio Pharmaceuticals is a biotechnology company dedicated to promoting the development of DNA medicines.
https://inf.news/en/science/8a969da978f3a9c2b0561d83157a7ca9.html
P2 DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine INO-3112 and MAb Durvalumab in Treating Patients With 21 Recurrent or Metastatic Human Papillomavirus Associated Cancers
https://clinicaltrials.gov/ct2/history/NCT03439085?A=13&B=14&C=merged#StudyPageTop
Ino reacquires the rights to INO-3112, may license out again. The deal, originally signed in 2015, was worth $27.5M upfront with $700M in biobucks down the line. Inovio has managed to pick up a couple M dollars through the partnership.
Sponsors and Collaborators:
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
MedImmune will also continue providing financial support for an externally sponsored research study of MEDI0457 (3112) with The UT MD Anderson Cancer Center until study completion.
Overall Status: Recruiting => Active, not recruiting
Primary Completion: December 31, 2021 => 2022 [Anticipated]
Study Completion: December 31, 2022 [Anticipated]
Last Update Submitted that
Met QC Criteria: December 1, 2020 => February 11, 2022
21 Conditions or Diseases:
Human Papillomavirus-16 Positive
Human Papillomavirus-18 Positive
Metastatic Malignant Neoplasm
Recurrent Anal Canal Carcinoma
Recurrent Cervical Carcinoma
Recurrent Malignant Neoplasm
Recurrent Penile Carcinoma
Recurrent Vaginal Carcinoma
Recurrent Vulvar Carcinoma
Refractory Malignant Neoplasm
Stage IV Anal Cancer AJCC v8
Stage IV Cervical Cancer AJCC v8
Stage IV Penile Cancer AJCC v8
Stage IV Vaginal Cancer AJCC v8
Stage IV Vulvar Cancer AJCC v8
Stage IVA Cervical Cancer AJCC v8
Stage IVA Vaginal Cancer AJCC v8
Stage IVA Vulvar Cancer AJCC v8
Stage IVB Cervical Cancer AJCC v8
Stage IVB Vaginal Cancer AJCC v8
Stage IVB Vulvar Cancer AJCC v8
MedImmune is currently conducting a P2 clinical trial of MEDI0457 in patients with head and neck squamous cell carcinomas (HNSCC). MedImmune has completed the final data cut off for the trial and plans to complete the clinical study report by the end of 2022.
https://clinicaltrials.gov/ct2/show/NCT02163057?term=Inovio&draw=4&rank=22
“I think we’re going to submit to FDA a significant progress of data about the need for a fourth dose, and they need to make their own conclusions, of course, and then CDC also. … It’s clear that there is a need in an environment of omicron to boost the immune response,” Bourla said.
Bourla maintained that he’s remaining vigilant in creating effective vaccines. “I think the biggest question of all of us is how to stay ahead of the virus.”
He said Pfizer is working on developing a vaccine that prevents infection in addition to preventing hospitalizations and severe cases of the virus, adding that making long-lasting vaccines is also a priority.
“We can’t have vaccines every five, six months,” Bourla said. “We need to be able to move as soon as possible.”
3/11/22 Students trapped in quarantine beg for help online as China faces biggest Covid outbreak since 2020
https://amp.cnn.com/cnn/2022/03/11/china/china-covid-jilin-university-mic-intl-hnk/index.html
Hong Kong(CNN) — China is fighting its biggest Covid-19 outbreak since the early days of the pandemic, with discontent spreading on social media after one university cluster left students reportedly without access to bathrooms or drinking water.
The country reported 1,100 new locally-transmitted cases on Thursday -- which, though nowhere near the level seen in other nations, is considered high by China's standards. It marked the highest daily total since the virus emerged in Wuhan in 2020, prompting alarm among local and national leaders.
Throughout the pandemic, China has adhered to a strict zero-Covid policy that aims to stamp out all outbreaks and chains of transmission using a combination of border controls, mass testing, quarantine procedures and lockdowns.
Authorities fell back on these familiar tactics as cases began surging around the country last week, imposing targeted lockdowns for residents in high-risk areas and mandatory quarantine for close contacts.
In Shanghai, where infections are rising, the city government converted several apartments into centralized quarantine centers, forcing tenants to clear out all their belongings, according to several government notices seen by CNN.
Snap lockdowns have also trapped a growing number of residents, office workers and schoolchildren with little advance notice, keeping them in their workplaces or schools until everybody inside tests negative, according to local residents.
What Xi'an's chaotic lockdown reveals about China's uncompromising top-down bureaucracy
But more than two years into the pandemic, public patience with these measures -- especially when executed at speed and with little consideration for the human impact -- appears to be fraying.
At the Jilin Agricultural Science and Technology University in northeastern Jilin province, students took to social media to plead for help, saying they had been left to fend for themselves after a cluster was detected on campus.
In one widely-shared post on China's Twitter-like platform Weibo, a user claiming to be a student at the university complained that infected students had been isolated in libraries and academic buildings, "all breaking down and crying."
"Many students in my dormitory had fever, but counselors just gave us fever reducers and told us to sleep with a warm quilt," the user wrote on Thursday. "There is a serious shortage of daily necessities. Girls have no sanitary pads. Students are bleeding and hurting, crying and calling their families."
CNN has reached out to the university through its official Weibo account for comment. The school's official website, and any additional contact information, has been taken offline as of Friday.
The Weibo user added that students isolated in their dormitories found "their doors were sealed off and they can't even go to the dormitory's public toilet." When the students tried to call the government's Covid-19 control center, phone operators "refused to answer our questions," he said.
Many of the students were transferred to a separate quarantine facility on Thursday, with 30 buses deployed to take them from campus, the state-run Global Times reported.
The Weibo post went viral, with more than 2.6 million likes and 410,000 shares. Public outrage flooded the internet, with users calling for accountability from local officials. A related hashtag garnered more than 1.88 billion views on Weibo, according to the Global Times.
"From the school to the prevention and control institutions to the Jilin city government -- if there was one person who had the courage to assume responsibility, it would not have developed to the present situation," one Weibo post read.
Later that day, the city government said the secretary of the school's Chinese Communist Party committee had been removed from the position for negligence.
Surging cases
The current outbreak has spread to several dozen cities in 20 provinces, according to the National Health Commission. The biggest hotspots are Jilin and eastern Shandong province, while cases have also been reported in the capital, Beijing, as well as Shanghai.
The capital of Jilin province, Changchun, issued a city-wide lockdown on Friday, forbidding all 9 million residents from leaving their neighborhoods. Each household is only allowed to send one person to buy groceries every other day.
As the Jilin university cluster began to spread, Jilin city closed schools and entertainment spaces. Similar closures were imposed for all schools in the city of Qingdao, home to 10 million people in Shandong province, and Shanghai.
Several cities are fighting the highly transmissible Omicron variant, according to local health authorities.
Students line up for Covid-19 testing at Qingdao Agricultural University on March 7 in China's Qingdao city.
In Qingdao's Laixi area, students make up more than a quarter of the 776 cases confirmed since March 4. Authorities say the cluster has since spread to other provinces -- leading to 17 officials from Laixi being punished Thursday for allowing "loopholes" and alleged negligence.
China's zero-Covid strategy has put local governments under huge pressure to keep the virus at bay, and a slew of officials have been punished during previous rounds of local outbreaks.
As public frustration and sympathy for the students mounted, state media acknowledged that some sectors were showing "a certain level of fatigue toward the dynamic zero-Covid strategy, which could affect the outcome of the implementation of the current policy."
Some Chinese leaders and scientists have also hinted that China could move away from the strategy. Zero-Covid "will not remain unchanged forever," wrote Zeng Guang, the chief epidemiologist at China's Center for Disease Control and Prevention, on Weibo last week.
But that transition will not happen anytime soon, with experts urging caution amid the surging cases, and warning new variants could still arise. "There is no need to open the door at the peak of the global epidemic," Zeng said.
3/10/22 President Biden on Thursday designated Colombia as a major non-NATO ally during a visit to the White House by Colombian President Iván Duque.
"I've said for a long time Colombia is a keystone to our shared efforts to build a hemisphere as prosperous, secure and democratic," Biden said during a meeting with Duque and other White House officials.
"Today I'm proud to announce that I intend to designate Colombia a major non-NATO ally ... that's exactly what you are," he added. "This is a recognition of the unique and close relationship between our countries."
Colombia was previously considered a "global partner." But it becomes the latest of more than a dozen nations to be granted major non-NATO ally status, including South Korea, Australia, Argentina and Kuwait. Biden said earlier this year he would give Qatar major non-NATO ally status, and former President Trump previously gave the same designation to Brazil.
The designation makes it easier for those countries to purchase U.S. weapons and collaborate on other security issues.
Colombia has been a key partner of the United States in managing issues like migration in South America, particularly as scores of Venezuelans flee the country under Nicolás Maduro's leadership.
In October 2021, INOVIO signed a non-binding MOU with Colombia's Ministry of Health and Social Protection reflecting the intent to advance efforts to combat the pandemic and endemic threat posed by COVID-19 and to better prepare for future public health emergencies. The MOU creates a framework for collaboration by which INOVIO and the government can explore knowledge sharing, technology licensing, and capacity building that support developing and producing vaccines and other biopharmaceuticals in Colombia. The potential results of these efforts include developing local manufacturing capabilities for INOVIO's DNA medicines and related products and technologies.
Lassa Virus (LASV) is a highly pathogenic species of Old-World Arenavirus endemic to West Africa causing Lassa fever (LF), a potentially acute hemorrhagic disease, in infected individuals. LF is a zoonotic disease transmitted by direct or indirect contact with rodent hosts. It results in approximately 300,000–500,000 infections and nearly 5,000 deaths annually in West Africa, primarily documented throughout Nigeria and the Mano River Union (MRU) countries of Guinea, Sierra Leone, and Liberia (1–3). Secondary nosocomial transmission is also a serious route of infection in resource-deficient regions. Around 80-90% of infections are asymptomatic or mild, however, the mortality rate in hospitalized patients can reach 15% to 20% and upwards of 50% during epidemics (4). The uptick of LF in 16 Nigerian states during early 2021 constitutes the largest outbreak to date and recapitulates the need for a rapid response. Currently of the 6252 suspected LF cases, 1138 have been laboratory confirmed with 235 deaths, a case fatality rate (CFR) of 20.7% (5). Neurological sequelae, including encephalopathy and aseptic meningitis, and sensorineural hearing loss is common in recovered patients (6, 7).
https://www.frontiersin.org/articles/10.3389/fitd.2022.847598/full#B16
LASV is morphologically pleotropic and its genome consists of 4 genes separated into two genomic segments responsible for viral structure, replication, and host antiviral evasion. There are no approved vaccines for LF and while there are several candidates in development, the diversity of vaccine platforms lags compared to other neglected tropical diseases, primarily consisting of recombinant or chimeric viral vectors (3, 8–15) as well as a DNA vaccine (16, 17). Furthermore, deployment of most virally vectored vaccines in endemic regions will be a logistical challenge as maintaining a proper cold chain can be difficult (18). Protein subunits are a reliable vaccine platform and can be administered either as a homologous prime-boost regimen or as boosters for other vaccines when immunity to the viral vector used is a concern.
16. Cashman KA, Broderick KE, Wilkinson ER, Shaia CI, Bell TM, Shurtleff AC, et al. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation. Vaccines (Basel) (2013) 1:262–77. doi: 10.3390/vaccines1030262
Abstract
Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC) that expressed the LASV glycoprotein precursor gene (GPC). This plasmid was used to vaccinate guinea pigs (GPs) using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.
https://pubmed.ncbi.nlm.nih.gov/26344112/
17. Jiang J, Banglore P, Cashman KA, Schmaljohn CS, Schultheis K, Pugh H, et al. Immunogenicity of a Protective Intradermal DNA Vaccine Against Lassa Virus in Cynomolgus Macaques. Hum Vaccin Immunother (2019) 15:2066–74. doi: 10.1080/21645515.2019.1616499
Abstract
Lassa virus (LASV) is a hemorrhagic fever virus of the Arenaviridae family with high rates of mortality and co-morbidities, including chronic seizures and permanent bilateral or unilateral deafness. LASV is endemic in West Africa and Lassa fever accounts for 10-16% of hospitalizations annually in parts of Sierra Leone and Liberia according to the CDC. An ongoing outbreak in Nigeria has resulted in 144 deaths in 568 cases confirmed as LASV as of November 2018, with many more suspected, highlighting the urgent need for a vaccine to prevent this severe disease. We previously reported on a DNA vaccine encoding a codon-optimized LASV glycoprotein precursor gene, pLASV-GPC, which completely protects Guinea pigs and nonhuman primates (NHPs) against viremia, clinical disease, and death following lethal LASV challenge. Herein we report on the immunogenicity profile of the LASV DNA vaccine in protected NHPs. Antigen-specific binding antibodies were generated in 100% (6/6) NHPs after two immunizations with pLASV-GPC. These antibodies bound predominantly to the assembled LASV glycoprotein complex and had robust neutralizing activity in a pseudovirus assay. pLASV-GPC DNA-immunized NHPs (5/6) also developed T cell responses as measured by IFN? ELISpot assay. These results revealed that the pLASV-GPC DNA vaccine is capable of generating functional, LASV-specific T cell and antibody responses, and the assays developed in this study will provide a framework to identify correlates of protection and characterize immune responses in future clinical trials.
https://pubmed.ncbi.nlm.nih.gov/31071008/
3/8/22 New class of killer T cells may prevent autoimmune diseases
Study identifies human counterparts to mouse cells that quell rogue immune response
https://www.science.org/content/article/new-class-killer-t-cells-may-prevent-autoimmune-diseases
The price for a vigilant immune system that can pounce on tumor cells or pathogens is occasional friendly fire—an autoimmune attack. Scientists have now identified a new type of human T cell that quells assaults on healthy tissues, a finding that could suggest treatments for conditions as diverse as lupus and cancer. “It’s a major step forward in understanding how the immune response and autoimmunity are regulated,” says immunologist Harvey Cantor of the Dana-Farber Cancer Institute, who wasn’t involved in the work.
Immunologists already knew mice and people deploy one type of regulatory T cell—a subset called Tregs that sports the protein CD4—and suppresses autoimmune attacks. The newer enforcers belong to a category of T cells distinguished by a different surface protein, CD8. CD8 T cells are best known for killing infected or cancerous cells, but in mice some of them also kill T cells that orchestrate autoimmune reactions. Although researchers have long suspected humans have similar cells, nobody had confirmed their existence.
One obstacle was that humans don’t make the distinctive receptors that mark the subset of CD8 cells in mice. However, some human CD8 T cells flaunt comparable receptors, the KIR proteins. To determine whether these human cells are immune inhibitors, Jing Li, a postdoc in the lab of immunologist Mark Davis at Stanford University’s School of Medicine, and colleagues measured their abundance in patients with autoimmune diseases such as multiple sclerosis, lupus, and celiac disease. The cells were more common in blood from patients than in blood from healthy people, the team reports online today in Science. Tissue samples revealed they congregated in parts of the body damaged by the autoimmune attack, such as the joints in people with rheumatoid arthritis and the small intestine in people with celiac disease.
The researchers detected similar surges of the KIR-producing T cells in people fighting infections, especially the pandemic coronavirus. In 56 COVID-19 patients, “We saw the KIR-positive cells going through the roof,” Davis says. And the sicker COVID-19 patients were, the more of the cells they harbored. The cells’ numbers also shot up in patients with influenza, the team found.
To investigate the cells’ role in autoimmunity, the scientists homed in on celiac disease, which is triggered by the gluten proteins in bread and other grain-based foods. In patients with the condition, so called helper T cells recognize gluten proteins such as gliadin and then spill molecules that promote inflammation. But in cell culture studies, Li and colleagues found, human CD8 T cells carrying KIR proteins killed the gliadin-detecting helper T cells. “That really opened up a window for us to understand the biology of these [KIR+] cells,” Li says.
To find out how much protection the cells provide against autoimmunity, Li and her colleagues analyzed genetically altered mice that have 50% to 75% fewer of the suppressive CD8 cells than normal. After exposure to certain viruses that can trigger autoimmune disease, the rodents developed signs of damage such as kidney inflammation. In contrast, control mice with a full complement of suppressive CD8 T cells didn’t show evidence of autoimmune diseases after infections.
Cantor and other scientists are convinced the team has fingered the long-sought human counterparts to the rodent immune regulators. “The paper provides really solid data that these cells exist in humans,” says immunologist Nu Zhang of the University of Texas Health Science Center, San Antonio. They may have remained obscure because they “are rare and are easily missed,” accounting for only about 5% of CD8-positive T cells, Davis says.
Immunologist Stephen Jameson of the University of Minnesota Medical School says approaches that increase the cells’ numbers abundance might help soothe difficult-to-treat autoimmune illnesses such as celiac disease. It’s also possible, he adds, that the cells are “sitting in tumors” and shielding them from immune attacks, in which case reducing the cells' could unleash a person’s immune system to fight cancer. Researchers have attempted to harness the traditional, CD4-carrying Tregs for therapies, but no treatments have been approved, Cantor notes. “The hope is that with this new set of regulatory cells, we can use them more efficiently.”
A key question is why the immune system needs another type of suppressive T cell when it already has Tregs. But Tregs are generalists that inhibit a variety of immune cells without killing them. Davis posits that the KIR-positive CD8 cells target particular T cells that switch on during an assault by a pathogen. Although these freshly activated T cells help clear the invaders, they can also attack healthy tissues. The KIR subclass serves as a “SWAT team” to kill off these potentially ruinous T cells once an infection is quelled, Davis proposes.
The explosion of KIR-positive CD8 T cells the researchers detected in patients with autoimmune diseases or COVID-19 may reflect an attempt to rein in destructive immune reactions—the immune overreaction to the novel coronavirus is what kills many COVID-19 patients in the end. How the suppressive CD8 cells distinguish T cells with self-destructive tendencies is one of the mysteries scientists still need to answer.
3/10/22 How mRNA and DNA Vaccines Could Soon Treat Cancers, HIV, Autoimmune Disorders and Genetic Diseases
How long have gene-based vaccines been in development?
This same strategy can be applied to the elimination of chronic infections like HIV, hepatitis B and herpes. These viruses infect the human body and stay in the body forever unless the immune system eliminates them. Similar to the way nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.
What is the status of these vaccines?
Some of the very first clinical trials of nucleic acid vaccines happened in the 1990s and were for cancer, particularly for melanoma.
Today, there are a number of ongoing mRNA clinical trials for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and others, and there have been some promising outcomes. Moderna recently announced promising results with its phase 1 trial using mRNA to treat solid tumors and lymphoma
There are also a lot of ongoing trials looking at cancer DNA vaccines, because DNA vaccines are particularly effective in inducing T cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer caused by human papilloma virus in women using a DNA vaccine.
Can nucleic acid vaccines treat autoimmune disorders?
Autoimmune disorders occur when a person’s immune cells are actually attacking a part of the person’s own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells are attacking myelin, a protein that coats the nerve cells in your muscles.
The way to eliminate an autoimmune disorder is to modulate your immune cells to prevent them from attacking your own proteins. In contrast to vaccines, whose goal is to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to dampen the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly tweaked genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce T regulatory cells that specifically suppressed only the T cells that were attacking myelin.
Any other applications of the new vaccine technology?
The last application is actually one of the very first things that researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born missing certain genes. The goal with gene therapy is to supply cells with the missing instructions they need to produce an important protein.
A great example of this is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the feasibility of essentially replacing the missing gene and allowing someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms could disappear, at least temporarily. The mRNA would not persist very long in the human body, nor would it integrate into people’s genomes or change the genome in any way. So additional doses would be needed as the effect wore off.
Research has shown that this concept is feasible, but it still needs some work.
Deborah Fuller, Professor of Microbiology, School of Medicine, University of Washington
https://www.daily-remedy.com/how-mrna-and-dna-vaccines-could-soon-treat-cancers-hiv-autoimmune-disorders-and-genetic-diseases/
3/9/22 NEJM: BACKGROUND
Waning of vaccine protection against coronavirus disease 2019 (Covid-19) and the emergence of the omicron (or B.1.1.529) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to expedited efforts to scale up booster vaccination. Protection conferred by booster doses of the BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar, as compared with protection conferred by the two-dose primary series, is unclear.
METHODS
We conducted two matched retrospective cohort studies to assess the effectiveness of booster vaccination, as compared with that of a two-dose primary series alone, against symptomatic SARS-CoV-2 infection and Covid-19–related hospitalization and death during a large wave of omicron infections from December 19, 2021, through January 26, 2022.
RESULTS
In a population of 2,239,193 persons who had received at least two doses of BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine, those who had also received a booster were matched with persons who had not received a booster.
Booster effectiveness against symptomatic omicron infection, as compared with that of the primary series, was 49.4% (95% CI, 47.1 to 51.6). Booster effectiveness against Covid-19–related hospitalization and death due to omicron infection, as compared with the primary series, was 76.5% (95% CI, 55.9 to 87.5). BNT162b2 booster effectiveness against symptomatic infection with the delta (or B.1.617.2) variant, as compared with the primary series, was 86.1% (95% CI, 67.3 to 94.1).
Among the mRNA-1273–vaccinated persons, booster effectiveness against symptomatic omicron infection, as compared with the primary series, was 47.3% (95% CI, 40.7 to 53.3). Few severe Covid-19 cases were noted in the mRNA-1273–vaccinated cohorts.
CONCLUSIONS
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death. (Funded by Weill Cornell Medicine–Qatar and others.)
STUDY POPULATION, BNT162B2 VACCINE
Between January 5, 2021, and January 26, 2022, a total of 1,299,010 persons received at least two doses of BNT162b2 vaccine and 281,093 of those persons received a third (booster) dose of that vaccine. The median date of the first dose was May 3, 2021; the median date of the second dose was May 24, 2021; and the median date of the third dose was December 14, 2021 (Fig. S1). The median time between the first and second doses was 21 days (interquartile range, 21 to 22), and the median time between the second and booster doses was 249 days (interquartile range, 232 to 270).
RESULTS
EFFECTIVENESS OF BNT162B2 BOOSTER AGAINST OMICRON VARIANT
The median follow-up time was 22 days (interquartile range, 12 to 38 days) in the booster cohort and 21 days (interquartile range, 11 to 38 days) in the nonbooster BNT162b2 cohort (Fig. S1). A total of 17,745 infections were recorded in the booster cohort 8 days or more after receipt of the booster (Figure 1 and Table S3). Twelve of these infections progressed to severe Covid-19, but none progressed to critical or fatal disease. A total of 25,266 infections were recorded in the nonbooster cohort. Of these infections, 45 progressed to severe Covid-19, 4 progressed to critical Covid-19, and none progressed to fatal Covid-19.
STUDY POPULATION, MRNA-1273 VACCINE
Between January 24, 2021, and January 26, 2022, a total of 890,619 persons received at least two doses of mRNA-1273 vaccine and 92,829 received a third (booster) dose of that vaccine. The median date of the first dose was May 28, 2021; the median date of the second dose was June 27, 2021; and the median date of the third dose was January 1, 2022 (Fig. S1). The median time between the first and second doses was 28 days (interquartile range, 28 to 30 days), and the median time between the second and booster doses was 232 days (interquartile range, 211 to 250 days).
RESULTS
EFFECTIVENESS OF MRNA-1273 BOOSTER AGAINST OMICRON VARIANT
The median follow-up time was 18 days (interquartile range, 8 to 32 days) in the booster cohort and 17 days (interquartile range, 8 to 31 days) in the nonbooster mRNA-1273 vaccine cohort (Fig. S1). A total of 3720 infections were recorded in the booster cohort 8 days or more after receipt of the booster (Figure 1 and Table S3). None of these infections progressed to severe, critical, or fatal Covid-19. A total of 4590 infections were recorded in the nonbooster cohort. Three of these infections progressed to severe Covid-19, but none progressed to critical or fatal Covid-19.
Discussion
BNT162b2 booster vaccination was associated with an 86.1% reduction in the incidence of symptomatic delta variant infection and a 49.4% reduction in the incidence of symptomatic omicron infection. With the mRNA-1273 booster, the reduction in the incidence of symptomatic infection with the omicron variant was similar at 47.3%. Fewer cases of severe Covid-19 were observed in the booster cohorts than in the nonbooster cohorts, which is consistent with the strong protection against hospitalization and death associated with the booster. Moreover, cases of severe Covid-19 were rare in both the booster and nonbooster cohorts despite the large number of infections. These findings affirm the durability of vaccine protection against hospitalization and death several months after receipt of the second dose.1,2
In the context of a global expansion of the omicron variant and the dwindling incidence of the delta variant, these findings may suggest that a longer-term strategy for a global response is the development and administration of a new generation of broadly effective vaccines rather than continuing with a strategy of repeated booster vaccination with existing vaccines. Pan-coronavirus vaccines35 would target a broad range of existing and future SARS-CoV-2 variants.
The effectiveness of the BNT162b2 booster, as compared with that of the two-dose primary series, was slightly higher than that of the mRNA-1273 booster. This may be explained by the higher baseline mRNA-1273 vaccine effectiveness and slower waning of effectiveness after the second dose.2,10,11 Possibly because of less waning, the effectiveness of both mRNA vaccines, as compared with that of the two-dose primary series, was lower in persons who had received the booster 8 months or less after the second dose than in those who had received it more than 8 months after the second dose.
The estimates of effectiveness of the BNT162b2 and mRNA-1273 vaccines against the delta and omicron variants are broadly consistent with the growing evidence of the effectiveness of mRNA vaccines against these variants in other countries.22-24,36-39 However, in our study, the effectiveness of boosters was compared with that of the two-dose primary series; we did not compare the outcomes among persons who received boosters with those among unvaccinated persons. Nevertheless, with the waning of vaccine protection against infection over time after the second dose1,2 — and more so against infection with the omicron variant36 — the effectiveness of boosters as compared with that of the primary series should be only slightly lower than the protection afforded by boosters as compared with no vaccination.
https://www.nejm.org/doi/full/10.1056/NEJMoa2200797
3/8/22 Global community comes together in support of 100 Days Mission and pledges over $1.5 billion for CEPI’s pandemic-busting plan
The UK Government pledged £160 million (US$211 million) to CEPI. Other top donors included the governments of Japan, Norway, USA, Germany, Australia, the Bill & Melinda Gates Foundation and Wellcome. G20 President Indonesia reaffirmed its support for CEPI with a pledge of $5m. Additional pledges were made at the Summit, and further commitments and donations are expected to follow in the coming months.
CEPI’s plan will reduce the risk posed by epidemics and pandemics by developing vaccines for known disease threats (such as Lassa fever, MERS and Nipah virus), and build on the scientific advances made during COVID-19 to prepare in advance for ‘Disease X.
The funds raised so far put CEPI on the path to raising the $3.5 billion it needs over the next five years to fund its pandemic-busting plan. CEPI’s plan will reduce the risk posed by epidemics and pandemics by developing vaccines for known disease threats (such as Lassa fever, MERS and Nipah virus), and build on the scientific advances made during COVID-19 to prepare in advance for ‘Disease X’- the threat of an unknown pathogen with pandemic potential. The funding committed today will also bolster CEPI’s work to develop the next generation of globally accessible COVID-19 vaccines, including ‘variant-proof’ COVID-19 vaccines, as well as vaccines that provide broad protection against all Betacoronaviruses.
Central to the plan is CEPI’s ambition – supported by the G7 and G20 – to compress the time taken to develop safe, effective, globally accessible vaccines against emerging diseases to as little as 100 days.
3/9/22 European stocks rally on best day in nearly two years as Ukraine’s president cools to NATO membership
Volodymr Zelensky told ABC News on Tuesday that “I have cooled down regarding the question” of NATO membership and said he was open to dialogue on the fate of Eastern Ukraine republics, Donetsk and Lugansky, that Russia recognizes as independent.
U.K. Prime Minister Boris Johnson this week said Ukraine had no “serious prospect” of NATO membership. Russia’s and Ukraine’s foreign ministers are due to meet Thursday in Turkey.
Exercise RSU (zero dollar strike price) and Hold as JK, LH, PK believe in LT upside. Had to pay tax upfront for the immediate gain. Very Bullish!
Each restricted stock unit represents a contingent right to receive one share of common stock. The vesting schedule for the 191,100 restricted stock units is as follows: 63,700 shares vested on March 8, 2020; 63,700 shares vested on March 8, 2021; 63,700 shares vested on March 8, 2022. Vested restricted stock units can be settled in shares of common stock, cash or a combination of both.
SEC Form 4: Kim Jong Joseph covered exercise/tax liability with 18,142 shares and converted options into 63,700 shares, increasing direct ownership by 4% to 1,322,938 units (tax liability)
https://quantisnow.com/insight/2549324
1. SEC Form 4: Humeau Laurent converted options into 19,900 shares and covered exercise/tax liability with 6,882 shares, increasing direct ownership by 16% to 95,605 units (for tax liability)
https://quantisnow.com/insight/2549298
2. SEC Form 4: Kim Jong Joseph covered exercise/tax liability with 18,142 shares and converted options into 63,700 shares, increasing direct ownership by 4% to 1,322,938 units (tax liability)
https://quantisnow.com/insight/2549324
3. SEC Form 4: Kies Peter converted options into 21,466 shares and covered exercise/tax liability with 11,287 shares, increasing direct ownership by 7% to 150,957 units to cover withholding tax
https://quantisnow.com/insight/2549340
Thurs 5/26/22 11:00 am ET INO-4800 – A DNA based Vaccine Against COVID-19
2nd Genetic Vaccine Development for Infectious Disease, Boston
Track B: Optimizing Clinical Translation & Development
Kate Broderick
Senior Vice President, R&D, INOVIO
Synopsis
Demonstrating efficacy in animal challenge models
Understanding phase 3 immunogenicity and safety profile
Proof of thermo stability of DNA vaccines and enhanced delivery through electroporation
Track A: Advancing Pre-Clinical Development & Discovery
11:00 am Optimizing DNA Vaccines Against Emerging Infectious Diseases
Ami Patel
Research Assistant Professor, The WISTAR Institute
Synopsis
Understanding DNA vaccine design and insight into mechanism of action
Demonstrating DNA vaccine preclinical studies
immunogenicity and protection in animal models
Understanding what constitutes next generation DNA vaccines and future outlook
https://genetic-vaccine-development.com/whats-on/day-two/
3/8/22 China is making progress in the development of nucleic acid vaccines for COVID-19, with a mRNA vaccine and a DNA vaccine in phase three clinical trials overseas, Wang Zhigang, Minister of Science and Technology, said on the sidelines of the ongoing two sessions on Tuesday.
Wang did not provide specific information about the vaccines. At the moment, China has granted conditional market approval to five vaccines, including three inactivated vaccines, one adenovirus vector vaccine and one recombinant protein subunit vaccine.
China has also approved one neutralizing antibody treatment for COVID-19 and Chinese scientists are researching drugs that may work on multiple COVID-19 strains including Delta, Omicron and other mutated variants, he said.
Meanwhile, China is also exploring new methods to administer COVID-19 vaccines, such as by inhalation or via nasal spray. "They are showing good progress," Wang said.
"The more tools for tackling COVID-19 that science and technology can provide, the better our anti-epidemic measures can become," he said.
https://www.chinadaily.com.cn/a/202203/08/WS6226e3f3a310cdd39bc8b2f3.html
3/9/22 obx4me2 said “I'm in P2. Confirmed unblinded trial. I have never had covid or covid symptoms. I never got omnicron. No covid infections. I do have INO-4800 TCELLs.
First dose was December 2020 second dose 28 days later January 2021.
Trial was unblinded and my clinic location confirmed. I got real vaccine INO-4800. Now I know I really did get INO-4800 like I believed all along.”
3/9/22 Nature Comms: Viral load reduction effectiveness of SARS-CoV-2 BNT162b2 mRNA booster vaccine wanes with time.
The findings of the study demonstrated 5,229 infections in unvaccinated individuals, 16,038 BTIs in COVID-19 second-dose-vaccinated individuals, and 1,390 BTIs in COVID-19 booster-dose-vaccinated individuals.
Multivariable linear regression analysis demonstrated that COVID-19 second dose-vaccinated individuals showed Ct regression coefficients of 4.2 for BTIs, post 7-30 days of second-vaccine dose compared to unvaccinated individuals. The regression coefficient decayed over time and vanished at six months or longer post-vaccination (for RdRP, N, and E gene).
COVID-19 booster vaccination increased Ct value by 2.7 for BTIs post 7-30 days of booster dose which corresponded to a six-fold decrease in the viral load. However, the effectiveness of the booster vaccine in reducing the viral load for BTIs declined rapidly to 1.3 and 0.8 post 31-60 days and 61-120 days of a booster dose, respectively.
The researchers applied the time differential model and observed a difference of 2.6 and 1.4 between the Ct values of infections in the first (7-30 days) and second (31-60 days) time bins, post-second dose and booster dose, respectively. These differences corresponded to a similar reduction in Ct values within a month by 62% and 52% post second and booster dose, respectively.
Conclusion
This study demonstrated the rapid waning of the effectiveness of the SARS-CoV-2 BNT162b2 mRNA booster vaccine in reducing viral loads within months post booster dose administration. The rate and magnitude of the reduction in the vaccine effectiveness post-booster dose mirrored the decline observed post-second vaccination dose. This decline in the effectiveness of booster dose possibly affects the community-level transmission of the SARS-CoV-2.
the study only considered the SARS-CoV-2 Delta-variant-dominant period, and additional data to understand the waning immunity during the dominance of the SARS-CoV-2 Omicron variant are needed.
researchers retrieved cycle threshold (Ct) values of SARS-CoV-2 RT-qPCR tests of all COVID-19-positive patients tested at the Maccabi Healthcare Services (MHS) Central Laboratory from 28 June, 2021, to 29, November, 2021.
Nasopharyngeal swab samples of patients were collected and Ct values for three SARS-CoV-2 genes – envelope (E), nucleocapsid (N), and ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) genes
https://www.news-medical.net/news/20220309/Viral-load-reduction-effectiveness-of-SARS-CoV-2-BNT162b2-mRNA-booster-vaccine-wanes-with-time.aspx
SYDNEY, March 9 (Xinhua) -- Despite taking a backseat due to widespread flooding and record rains across Australia's east, states have continued to battle against the spread of COVID-19.
In the 24 hours to 4:00 p.m. local time on Tuesday, the Australian state of New South Wales recorded 13,179 new cases and nine deaths. Cases in the state have seen an uptick over the last week, with daily cases remaining below 10,000 in late February and into some of early March.
NSW Health reports there are 1,038 people in hospital with the virus, including 39 in intensive care and 16 are ventilated. Over the last week, hospitalization numbers have remained steady at around 1,000 in the state.
NSW Health announced on Tuesday that many of the state's testing facilities had been closed due to flooding, as they urged residents to check the status of a clinic before traveling.
Meanwhile, the Australian state of Queensland, the worst hit by floods and torrential weather, has also recorded 4,801 new locally acquired cases and 13 deaths in the 24 hours to 7:00 p.m. local time Tuesday.
The Australian state of Victoria reported 7,081 new cases and 9 deaths in the 24 hours to midnight. However, the number of patients requiring hospitalization has steadily declined from 262 to 196 over the past week.
According to the Australian Department of Health, Australia on Tuesday breached 3 million total COVID-19 cases since the beginning of the pandemic and has seen a total of 5,464 deaths from the virus
http://www.xinhuanet.com/english/asiapacific/20220309/f4c0d445a2de40b8bac8caf2dd168731/c.html
3/8/22 Philippines DOH PROCUREMENT OF 500,000 doses HEPATITIS B (RECOMBINANT DNA) VACCINE
Submission and Opening of Bids: 23 February 2022; 9:00 A.M.16 To March 2022; 9:00 AM
Total Approved Budget for the Contract (ABC): PhP 9,150,000.00
Bid Bulletin is being issued toannounce the new schedule of the Submission and Opening of Bids,amend or modify the bidding documents posted in the PhilGEPS and DOH websites, and to respond to the letter of Genpharm,Inc. for the Procurement of Hepatitis B (Recombinant DNA)Vaccineunder IB No. 2022-047.ThisBid Bulletin shall form an integral part of the bidding documents. Listed below are the corresponding modifications/changes.
P1 DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection
Active, not recruiting
Record Verification: February 2021 => August 2021
Last Update Submitted that
Met QC Criteria: July 30, 2021t => August 12, 2021
Last Update Posted: August 2 => 13, 2021 [Actual]
Sponsors and Collaborators
National Cancer Institute (NCI)
Inovio Pharmaceuticals
Investigators
Principal Investigator: Jeffrey M Jacobson Mayo Clinic
PRIMARY OBJECTIVES:
I. To determine the safety profile of the HCV DNA vaccine, consisting of INO-8000 (HCV antigen DNA) alone or co-administered with INO-9012 (interleukin [IL]-12 adjuvant DNA) (DNA plasmid encoding interleukin-12 INO-9012).
II. To identify a dose of INO-9012 (IL-12 adjuvant DNA) for co-administration with INO-8000 (HCV antigen DNA) based on induction of HCV-specific interferon (IFN)-gamma production by peripheral blood mononuclear cells at 26 weeks compared to baseline in HCV-infected participants.
N01CN00042 ( U.S. NIH Grant/Contract )
P30CA015083 ( U.S. NIH Grant/Contract )
https://reporter.nih.gov/search/0rcpQYSM60KgZCKbFN8zWA/projects
https://clinicaltrials.gov/ct2/history/NCT02772003?A=23&B=24&C=merged#StudyPageTop
4/21/22 09:40 ET World Vaccine Congress: Inovio’s DNA COVID vaccine update
WASHINGTON DC, 18 - 21 APRIL 2022, World Vaccine Congress
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