Induction of Broadly Neutralizing H1N1 Influenza Antibodies by Vaccination

• Published in: Science (American Association for the Advancement of Science) 2010-08, Vol.329 (5995), p.1060-1064
• Main Authors: Wei, Chih-Jen, Boyington, Jeffrey C, McTamney, Patrick M, Kong, Wing-Pui, Pearce, Melissa B, Xu, Ling, Andersen, Hanne, Rao, Srinivas, Tumpey, Terrence M, Yang, Zhi-Yong, Nabel, Gary J
• Format: Article
• Language: English
• Subjects: Adenovirus; Animals; Antibodies; Antibodies, Neutralizing - biosynthesis; Antibodies, Neutralizing - immunology; Antibodies, Viral - biosynthesis; Antibodies, Viral - immunology; Biological and medical sciences; Cross Protection; Dating; DNA; Encoding; Female; Ferrets; Fundamental and applied biological sciences. Psychology; Genetic Vectors; H1N1 subtype influenza A virus; H3N2 subtype influenza A virus; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Humans; Hydroxyapatite; Immune system; Immunization; Immunization, Secondary; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H2N2 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza virus; Influenza, Human - immunology; Influenza, Human - prevention & control; Macaca mulatta; Male; Mice; Mice, Inbred BALB C; Microbiology; Mustela; Mutant Proteins - immunology; Neutralizing; Neutralizing antibodies; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Plasmids; Primates; Strain; Swine flu; Trimers; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Virology; Viruses
• ISSN: 0036-8075; 1095-9203
• 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 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as 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 the development of a universal influenza vaccine for humans.