Conventional and experimental vaccines against avian influenza

Avian influenza H5N1 virus, family Orthomyxoviridae, naturally persists in waterfowl and domestic bird reservoirs with sporadic outbreaks of highly pathogenic strains. Several human cases were reported during the 1997 H5N1 avian epidemic in Hong Kong, showing direct transmission from domestic poultry and the first occurrence of an H5 influenza subtype in humans. Highly pathogenic avian influenza (HPAI) H5N1 variants later re-emerged following years of circulation in wild bird reservoirs and new human cases were identified in Southeast Asia during 2003. Evidence suggests that the H5N1 virus is rapidly evolving and although HPAI H5N1 has not yet adapted for efficient human-to-human transmission, it is currently considered a major threat for a global influenza pandemic. The World Health Organization (WHO) and several nations have prioritized improving available inactivated or LAIV, and the development of alternative platforms against potential influenza outbreaks. While currently approved vaccines have been successful against influenza viruses of the same subtype, complete cross-protection has yet to be achieved. This chapter reviews different vaccine strategies against avian influenza H5N1, reflects on the requirements for effective vaccine development, and discusses the direction of future influenza vaccine research. The rapid development of several experimental platforms in recent years has enhanced protective efficacy and immunogenicity following immunization, additionally benefiting understanding of influenza virus pathogenesis. The most promising platforms have been evaluated successfully in ferrets and non-human primate models, with several candidates currently in human clinical trials. The objective of influenza vaccine research will be to develop a universal, single vaccine candidate capable of complete cross-protection against divergent influenza subtypes.