1976 and 2009 H1N1 Influenza Virus Vaccines Boost Anti-Hemagglutinin Stalk Antibodies in Humans

Background. Infection with pandemic H1N1 influenza A viruses (IAVs) containing hemagglutinin (HA) proteins with globular heads that differ substantially from seasonal strains results in a boost in broadly cross-reactive antibodies that bind to the HA stalk. Boosting these antibodies has become an attractive strategy for creating a universal IAV vaccine. Therefore, it was essential to determine whether vaccines containing H1N1 viruses whose head domains differ substantially compared to seasonal strains could also achieve this boost. Methods. Prospective samples of subjects who had received the A/New Jersey/1976 (NJ/76) vaccine and healthy, age-matched controls were assessed for the presence of anti-HA stalk antibodies before and after receiving the A/California/04/2009 (Cal/09) vaccine between October 2009 and January 2010. Results. Individuals who received either the NJ/76 vaccine or the Cal/09 vaccine experienced a robust boost in HA stalk-reactive, neutralizing antibodies similar to what has been observed in individuals infected with Cal/09. Conclusions. These results demonstrate that vaccines containing viruses whose HA head domains that differ substantially from seasonal strains are capable of boosting titers of HA stalk antibodies. Furthermore, anti-HA stalk antibodies elicited by vaccination appear to be long-lived and therefore could be targeted for the generation of a universal IAV vaccine.