Friday, November 22, 2013

FDA Approves Adjuvanted H5N1 Vaccine For National Stockpile


Since the H5N1 virus was first identified in 1996 it has expanded into more than 20 different clades and subclades, and new clades and variants continue to evolve. Credit - WHO

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With the recent emergence of H7N9 and MERS-CoV,  some may think of avian H5N1 influenza as `yesterday’s threat’,  but that virus continues to circulate – and mutate into new clades – in many places around the world.  Earlier this month in The Expanding Variants Of H5N1 we looked at an EID report on the emergence of three new variations of the H5N1 virus in Vietnam between 2009 and 2012.


And while the number of human H5N1 infections being reported in Indonesia, China, and Egypt have been much reduced over the past couple of years, Cambodia has seen more cases this year than their total over the 8 years before 2013 (see Nov 14th report Cambodian MOH Announces Two New H5N1 Cases.


Although some early experimental H5N1 vaccines were produced and stockpiled by the United States government in 2006 and 2007, the clades those shots were based on are no longer dominant.  Additionally, early human testing revealed a very poor immune response when using the standard antigen load of 15 ug.  In fact, it was discovered that it might take a whopping 12x’s the antigen (2 - 90 ug shots, 21 days apart) to produce a reasonable level of protection.


With a limited ability to produce H5N1 antigen in bulk, a requirement for 2-90 ug shots would dramatically reduce the number of vaccines that could be delivered in the first 6 to 12 months of a pandemic.


The solution offered was the inclusion of an adjuvant -  proprietary chemicals that are added to vaccines to increase the recipient’s immune response, and that can dramatically lower the amount of antigen needed in a vaccine. Since they are viewed by some as somewhat controversial, adjuvants were not used in flu vaccines in the United States during the 2009 H1N1 pandemic, but they were widely used in Canada and Europe.


While millions received adjuvanted vaccines during the 2009 pandemic without incident, a small number of children in Europe developed a rare neurological illness (narcolepsy) in the months after receiving the adjuvanted Pandemrix vaccine.


Although the adjuvant is being looked at, the actual cause of this illness has not been established.  The exact mechanism behind this Pandemrix-Narcolepsy link remains a medical mystery. Our understanding of this neurological disorder is very limited, as well.


In February of this year the UK’s HPA published a statement ( see Pandemrix Vaccine Linked To Childhood Narcolepsy In England) that found the absolute risk of a child developing narcolepsy from the adjuvanted Pandemrix flu shot appeared to be about 1 in 55,000. 

Over the past several years GSK has been moving through the approval process on their candidate monovalent, adjuvanted pandemic H5N1 influenza vaccine. Data published in November of 2012 indicated that they’d found a good immune response with their adjuvanted vaccine with just two doses of 3.75 ug, given 21 days apart. 


The adjuvant is provided in a separate vial, and is pre-mixed prior to injection.  You can view a Power Point Presentation on the FDA Website with the details of those trials at this link.



All of which brings us to a late Friday afternoon announcement from the FDA, that they have approved the first adjuvanted flu vaccine for the prevention of H5N1 influenza . This approval is for inclusion in the National Strategic Stockpile, not for commercial use, and is approved only for those over the age of 18.




For Immediate Release: Nov. 22, 2013

Media Inquiries: Jennifer Rodriguez, 301-796-8232,
Consumer Inquiries: 888-INFO-FDA,

FDA approves first adjuvanted vaccine for prevention of H5N1 avian influenza

Vaccine to supplement National Stockpile, not intended for commercial availability

The U.S. Food and Drug Administration today approved the first adjuvanted vaccine for the prevention of H5N1 influenza, commonly known as avian or bird flu. The vaccine, Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, is for use in people 18 years of age and older who are at increased risk of exposure to the H5N1 influenza virus.

Avian influenza is an infectious disease of birds caused by certain influenza A viruses. Most avian influenza A viruses do not infect people. However some viruses, such as H5N1, have caused serious illness and death in people outside of the U.S., mostly among people who have been in close contact with infected and ill poultry. When people do become infected with H5N1, about 60 percent die, according to the World Health Organization. H5N1 is an influenza virus with pandemic potential because it continues to infect wild birds with occasional outbreaks of influenza disease in poultry populations, and most humans have no immunity to it.


“This vaccine could be used in the event that the H5N1 avian influenza virus develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the globe,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research. “Vaccines are critical to protecting public health by helping to counter the transmission of influenza disease during a pandemic.”


The H5N1 avian influenza vaccine is not intended for commercial availability. The U.S. Department of Health and Human Services has purchased the vaccine from the manufacturer, ID Biomedical Corporation of Quebec, Quebec City, Canada (a subsidiary of GlaxoSmithKline Biologicals), for inclusion within the National Stockpile for distribution by public health officials if needed.


The vaccine is made using an egg-based manufacturing process, which is also used for ID Biomedical Corporation’s seasonal influenza vaccine, FluLaval. It contains the adjuvant AS03, an oil-in-water emulsion. An adjuvant is a substance incorporated into some vaccines to enhance or direct the immune response of the vaccinated individual. The adjuvant makes it possible to use a small amount of influenza protein per dose of vaccine to elicit the desired immune response in an individual to prevent influenza disease. Reducing the amount of influenza protein per dose helps to increase the total number of doses of a safe and effective vaccine available for the public during a pandemic.


The H5N1 component and the AS03 adjuvant component are supplied in two separate vials, which must be combined prior to use. The vaccine is administered via intramuscular injection in two doses, 21 days apart.


The evaluation of safety compared approximately 3,400 adults 18 years of age and older who received the vaccine to about 1,100 adults who received placebo in a multi-center study. The most common side effect reported during the clinical studies among the vaccine recipients was injection site pain. Muscle aches, headache, fatigue and injection site redness and swelling were also common. To determine how well the vaccine works, the immune response was evaluated in about 2,000 of the vaccinated adults. The results showed that 91 percent of individuals between the ages of 18 and 64 years and 74 percent of individuals 65 years and older who received the two-dose regimen developed antibodies at a level that is expected to reduce the risk of getting influenza.


The manufacturer will collaborate with the FDA and other U.S. governmental agencies on plans to collect additional safety and effectiveness data through U.S. government-sponsored studies of the vaccine, in the event that it is used during an H5N1 influenza virus pandemic.

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