Immune correlates to an inactivated H5N1 vaccine in humans

An effective vaccine would be the first choice for protection against future pandemic influenza infection. Hundreds of millions of vaccine doses would be required to prevent the first wave of the disease in a pandemic. However, because influenza virus can mutate quickly, one cannot predict exactly which strain of influenza virus will be next the pandemic virus. Therefore, a vaccine would not only have to be effective but would also have to be made in a very short period of time. The current avian flu vaccine (H5N1) is poorly immunogenic in humans and has to be used at a 10-fold higher doses than the seasonal influenza vaccines and more than one shot is needed to reach protective levels of antibody. The amount of the vaccine required is therefore far beyond the present worldwide manufacturing capacity and current candidate vaccines may be too slow in stimulating protection. The simplest way to solve this problem would be to lower the dose and number of shots required for protection by increasing the immunogenicity of the vaccine. This research project aims to study how to enhance the immune responses to avian influenza vaccines in a Phase II clinical trial. The outcome of this study will help to develop an effective vaccine requiring a lower dose to protect against H5N1 infection.

Highly pathogenic strains of avian influenza (H5N1) virus from Asia, which have a near 50% death rate in infected humans, pose a potential threat to public health should they start transmitting between humans. An effective vaccine that induces a long-lasting protective immunity against this virus is urgently needed. However, our knowledge of the mechanisms governing protective immunity to influenza A virus is incomplete, particularly the immunogenicity of avian influenza virus in humans. The aim of this proposal, involving collaboration with two Chinese research institutes, is to study the immunogenicity of an inactivated H5N1 vaccine in a Phase II clinical trial. Our results will provide novel and invaluable information for designing safe and cost-effective vaccines for future pandemic influenza.