Broad cross-protective anti-hemagglutination responses elicited by influenza microconsensus DNA vaccine

Despite the routine development and distribution of seasonal influenza vaccines, influenza remains an important pathogen contributing to significant human morbidity as well as mortality each year. The seasonal variability of influenza creates a significant issue for vaccine development of seasonal strains that can afford protection from infection or disease based on serotype matching. It is appreciated that the globular head of the HA antigen contained in the vaccines generates antibodies that result in HAI activity that are a major correlates of the protection against a particular strain. Due to seasonal genetic changes in the HA protein, however, new vaccine strains are needed to be developed continually to match the new HA antigen of that seasons virus. A distinct advantage in seasonal vaccine development would be if a small group of antigens could be developed that could span many seasons without needed to be replaced due to this genetic drift. Here we report on a synthetic microconsensus approach that relies on a small collection of 4 synthetic H1HA DNA antigens which together induce broad protective HAI immunity spanning decades of H1 influenza viruses in mice, guinea pigs and non-human primates. The protective HAI titers induced by microconsensus immunogens are fully functional in vivo as immunized ferrets were completely protected from A/Mexico/InDRE4487/2009 virus infection and morbidity associated with lethal challenge. These results are encouraging that a limited easy-to-formulate collection of invariant antigens can be developed which can span seasonal vaccine changes allowing for continued immune protection.