Biotech Values

[Preciouslife1]

Nasal Hepatitis B Vaccine Elicits Robust Immunity With A Single Dose; Confers Major Advantages Over Traditional Vaccines

http://www.medicalnewstoday.com/articles/118194.php

A new study has shown that a nasal hepatitis B vaccine elicits a dramatic immune response in animals without requiring three vaccinations, sterile syringes or refrigeration-three factors that impede the delivery of current hepatitis B vaccines.

In the study, a single dose of the nasal vaccine triggered a protective response in animals roughly 450 times greater than that elicited by currently approved human vaccines.
The animal studies demonstrate a magnitude of immunity that has not been seen in advanced preclinical testing of other nasal vaccines, according to the scientists at the University of Michigan and NanoBio Corp.

Moreover, the mucosal vaccine produced three distinct types of immunity-mucosal, cellular and systemic-which enabled a rapid immune response that could kill virus-infected cells and prevent future infections. Traditional injected vaccines do not elicit mucosal or cellular immunity.

The study, reported in the online August 13 issue of the journal PLoS One (Public Library of Science), has critical implications for developing countries where hepatitis B presents a serious health threat, said James R. Baker Jr., M.D., lead author on the paper and a founder of NanoBio Corp. NanoBio is a spin-out from the University of Michigan and has exclusive rights to commercialize the vaccine technology.

Developing nations have difficulty providing proper refrigeration, sterile needles or three separate vaccinations, as are currently required. As a result of these challenges and despite the existence of effective vaccines, more than 400 million children and adults worldwide are infected, and more than a million people die from hepatitis B each year.

"We have developed a new vaccine that is extremely safe, easy to administer, and which rapidly builds protection against hepatitis B infection," said Baker. "The same vaccine platform has also been shown to elicit significant immune responses in animal studies with influenza, anthrax, smallpox, RSV and HIV. Plans are under way to begin testing in humans."

The vaccine platform and its associated research, funded in part by the Bill & Melinda Gates Foundation, represents a major departure from traditional vaccines on numerous levels.

Among its unique qualities, the mucosal vaccines are delivered directly to the lining of the nose where immune cells recognize the foreign antigen contained in the vaccine. This rapid stimulation of the immune system does not involve inflammatory chemicals as used in injected vaccines, which can cause pain and swelling at the site of vaccination. It also produces cellular immunity that is not seen with intramuscular vaccination.

"Patients who lack cellular immunity can build up the needed antibodies to eradicate viral particles in the blood and interstitial fluid, but they may not be able to remove infected cells where the virus hides," said Baker. "This is often the case with chronically infected patients, so our vaccine may be of particular benefit to this population of immune-compromised individuals."

Robust immunity aside, the mucosal vaccine also eliminates a number of logistical impediments that have stymied traditional vaccine use worldwide:

-- The nanoemulsion vaccine is safe and simple to produce, containing a mixture of oil, water, alcohol and two surfactants together with commercially available antigens

-- The nanoemulsion itself serves as the "adjuvant" to stimulate an immune response, demonstrating significant antigen-sparing properties

-- The formulation is extremely stable, allowing for long-term storage of 3 to 6 weeks or longer with potentially no refrigeration

-- Finally, a single-dose administration schedule enables rapid immunity against hepatitis B, whereas traditional injected vaccines usually require as many as three separate vaccinations over 6 months.

NanoBio is in various stages of testing its pipeline of nasal vaccines. Human testing of the influenza and hepatitis B vaccines are being planned for next year, and data from expanded ferret studies with the influenza vaccine are expected this quarter. Earlier influenza studies in ferrets demonstrated very robust immunity, suggesting significant antigen-sparing properties.

About NanoBio

NanoBio(R) Corp. is a privately held biopharmaceutical company focused on developing and commercializing anti-infective products and mucosal vaccines derived from its patented NanoStat(TM) technology platform. The company's lead product candidates are treatments for herpes labialis (cold sores), onychomycosis (nail fungus), acne and a broad platform of mucosal vaccines. The company's headquarters and laboratory facilities are located in Ann Arbor, Michigan.

Plus this also:

Nano Vaccine For Hepatitis B Shows Promise For Third World - Nanoemulsion Could Save More Lives By Removing Current Vaccines' Drawbacks

Chronic hepatitis B infects 400 million people worldwide, many of them children. Even with three effective vaccines available, hepatitis B remains a stubborn, unrelenting health problem, especially in Africa and other developing areas. The disease and its complications cause an estimated 1 million deaths globally each year.

In many poor countries, refrigerated conditions required for the current vaccines are costly and hard to come by. It's often difficult in the field to keep needles and syringes sterile. The need to have people return for the three shots currently required also limits success.

Now, a new vaccine that avoids these drawbacks has moved a step closer to human trials. Health researchers hope it will make it possible to immunize large numbers of children and adults in Africa, Asia and South America efficiently and safely.

Scientists at the Michigan Nanotechnology Institute for Medicine and Biological Sciences at the University of Michigan report that a novel, needle-less method for getting an immunity-stimulating agent into the body has proved non-toxic and able to produce strong, sustained immune responses in animal studies. The vaccine is based on a super-fine emulsion of oil, water and surfactants placed in the nose.

The research was supported by the Grand Challenges in Global Health initiative, which is funded by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, the Wellcome Trust and the Canadian Institutes of Health Research. The findings appear online in the journal PLoS ONE.

The nanoemulsion represents a new delivery method for an antigen already used in existing hepatitis B vaccines to activate the body's immune defenses.

"Our results indicate that needle-free nasal immunization, using a combination of nanoemulsion and hepatitis B antigen, could be a safe and effective hepatitis B vaccine, and also provide an alternative booster method for existing vaccines," says James R. Baker, Jr., M.D., the study's senior author and director of the institute. He also is Ruth Dow Doan Professor and allergy division chief in the U-M Department of Internal Medicine.

The nanoemulsion is made up of soybean oil, alcohol, water and detergents emulsified into droplets less than 400 nanometers in diameter.

The study suggests that the new type of hepatitis B vaccine will not have rigid cold storage requirements and could require fewer administrations than current vaccines, which require three shots given over a period of six months. Protective immunity with the new vaccine required only two immunizations in animals. The vaccine also avoids the risk of spreading needle-borne infections.

The nanoemulsion vaccine also avoids the temporary pain and redness that results after people get shots with the current vaccines, in which an irritating compound, alum, is used as an adjuvant, or enhancer of a vaccine's effect. There was no local inflammation at the nasal site of administration with the new vaccine.

This finding may be significant, because one of the major concerns for nasal administration of vaccines is that they can find their way to the olfactory bulb in the brain and cause side effects, says Paul E. Makidon, D.V.M., co-first author of the study and a U-M research fellow. "Our studies, however, indicate no inflammation and no evidence of the vaccine in the olfactory bulb," he says.

Baker's team has published earlier studies affirming the promise of nasal nanoemulsions as a strategy for smallpox, influenza, anthrax and HIV vaccines. The nanoemulsion technology is patented by U-M and licensed to Ann Arbor-based NanoBio Corporation. Baker is a founder and equity holder of NanoBio.

Research details:

The research team determined effective doses of the antigen and nanoemulsion. In results obtained in mice, rats and guinea pigs, the nanoemulsion vaccine proved effective at producing three types of immunity: systemic, mucosal and cellular. Further toxicity studies in rodents and dogs showed the vaccine was safe and well-tolerated.

The vaccine was as effective as current hepatitis B vaccines in eliciting systemic protective antibodies in the blood of animals. The nanoemulsion acted as an effective adjuvant, without the need for a traditional adjuvant or inflammatory compound as in the current hepatitis B vaccines.

In addition, the nanoemulsion vaccine produced sustained cellular immunity in Th1 cells, which could make the vaccine useful in treating people with chronic hepatitis B whose own cellular immune responses are inadequate.

The animals given the nasal nanoemulsion in the study also activated a third type of immunity, mucosal immunity, which is gaining recognition among immunologists as a key first-line response to infectious agents in diseases such as hepatitis B where mucosal tissues are involved in transmission. Baker and his team found the same effect of activating mucosal immunity that was seen in their previous studies of other nanoemulsion-based vaccines.

The researchers tested whether the vaccine could remain stable and effective even if not refrigerated. They found the nanoemulsion vaccine retained its effectiveness for six months when kept at 25 degrees Celsius (77 degrees Fahrenheit), and even was stable and effective for six weeks at 40 degrees C (104 degrees F). This suggests that refrigeration will not be needed for the final distribution of the vaccine in developing countries, making it easier to vaccinate underserved people.

Current studies are focused on developing the preclinical data required to enter human trials, Baker says. The researchers hope that the first human trial can begin within a year.

Additional U-M authors include: Anna U. Bielinska, Shraddha S. Nigavekar, Katarzyna W. Janczak, Jessica Knowlton, Alison J. Scott, Nicholas Mank, Zhengyi Cao, Sivaprakash Rathinavelu, Michael R. Beer, J. Erby Wilkinson, Luz P. Blanco and Jeffrey J. Landers.

Citation: PLoS ONE, http://dx.plos.org/10.1371/journal.pone.0002954

University of Michigan Health System



><)))*> "Grace be unto you and peace from Him who is and who was and who is to come." <*(((>< Laus Deo

The Vision that you glorify in your mind, the Ideal that you enthrone in your heart,this you will build your life by, this you will become