Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antibodies, Neutralizing / biosynthesis
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Antibodies, Neutralizing / immunology*
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Antibodies, Viral / biosynthesis
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Antibodies, Viral / immunology*
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Cross Protection*
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Female
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Ferrets
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Genetic Vectors
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Humans
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Immunization, Secondary
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Influenza A Virus, H1N1 Subtype / immunology*
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Influenza A Virus, H2N2 Subtype / immunology
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Influenza A Virus, H3N2 Subtype / immunology
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Influenza A Virus, H5N1 Subtype / immunology
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Influenza Vaccines / administration & dosage*
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Influenza Vaccines / immunology*
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Influenza, Human / immunology
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Influenza, Human / prevention & control
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Macaca mulatta
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Male
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Mice
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Mice, Inbred BALB C
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Mutant Proteins / immunology
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control
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Plasmids
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Vaccination
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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H1N1 virus hemagglutinin
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Hemagglutinin Glycoproteins, Influenza Virus
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Influenza Vaccines
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Mutant Proteins
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Vaccines, DNA