Avian Flu Diary: Vaccine: Safety & Immunogenicity Of H5N1 Vaccine Stored Up To 12 Years

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In the middle first decade of the 21st century, when we had only one avian flu virus of real concern (H5N1), many countries decided to stockpile millions of doses of vaccine (see Japan Considers Their Pre-Pandemic Vaccine Options) because the bird flu threat appeared imminent.

By the end of the decade, we'd had a pandemic - but from a swine origin H1N1 - not from H5N1, and many millions of doses of the vaccine were at, or approaching, their expiration point.

While some countries adopted a `use it, or lose it' policy, and administered the expiring vaccines (see Taiwan Offers Public Bird Flu Vaccinations) to volunteers, others simply disposed of the vaccine and lamented the lost investment.

A similar situation arose in 2009, with many countries facing the expiration of their stockpile of Tamiflu (oseltamivir), when the WHO Issued A Reprieve giving the go ahead to tack on a couple of extra years to the 5 year shelf life of the drug.

As has been discovered with many other drugs in our Strategic National Stockpile, expiration dates don't necessarily reflect the genuine life of a drug that is kept under the right conditions.

And now we have confirmation that H5N1 avian flu vaccines - and presumably others - previously deemed unusable after 3 years, likely remain both safe and effective for well over a decade.

Safety and immunogenicity of influenza A(H5N1) vaccine stored up to twelve years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS)Christine M.Oshansky^a JamesZhou^a YonghongGao^a Jo EllenSchweinle^a KarenBiscardi^a JenniferDeBeauchamp^b CorrinaPavetto^a AmyWollish^c BRITE Study Coordination Team¹ Richard J.Webby^b VittoriaCioce^a Ruben O.Donis^a Rick A.Bright^a

Abstract

Background
As part of the U.S. Department of Health and Human Services (HHS) Pandemic Influenza Plan preparedness and response strategy, the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) program was established by the Biomedical Advanced Research and Development Authority (BARDA) in 2005 with the goal of building and maintaining a stockpile of vaccines for influenza viruses with pandemic potential to vaccinate 20 million people in the critical workforce in the event of a pandemic.

The NPIVS program continuously monitors the integrity of influenza vaccine antigens and adjuvants stored within the stockpile. In addition to monitoring physical and chemical properties in stability studies, it is important to regularly assess the safety and immunogenicity of stockpiled vaccines and adjuvants to maintain preparedness for use in the event of an influenza pandemic.

Methods

BARDA conducted a randomized, double-blinded Phase 2 clinical study with the oldest stockpiled influenza A(H5N1) antigen, stored over the previous 10–12 years administered with or without MF59® adjuvant, stored over the previous 2–7 years at the time of vaccination.

Results

Stockpiled vaccines were well-tolerated, adverse events were generally mild, and there was no drop in immunogenicity to the oldest stockpiled A(H5N1) vaccine. Compared to unadjuvanted vaccine, greater peak antibody responses were observed in subjects who were vaccinated with MF59-adjuvanted vaccines, regardless of antigen dose. Vaccination with the A(H5N1) vaccine antigen also results in cross-reactive antibody responses to contemporary circulating strains of A(H5) influenza viruses.

Conclusions

The frequency, type, and severity of AEs observed during this study are similar to historical clinical study data with A(H5N1) vaccines and MF59 adjuvant indicating that a stockpiled A(H5N1) vaccine appears to remain safe and tolerable. The vaccines were immunogenic when administered as a two-dose vaccine regimen in healthy adults, despite extended storage of HA antigen or MF59 adjuvant within the NPIVS.