Induction of Broadly Neutralizing H1N1 Influenza Antibodies by Vaccination

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Science  15 Jul 2010:
DOI: 10.1126/science.1192517


The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 (rAd5) vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime-boost combination increased neutralization of diverse H1N1 strains from 1934 to 2007 compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for development of a universal influenza vaccine for humans.