title: A universal influenza A vaccine based on adenovirus expressing matrix-2 ectodomain and nucleoprotein protects mice from lethal challenge.
abstract: A universal influenza vaccine, designed to induce broadly cross-reactive immunity against current and future influenza A virus strains, is in critical demand to reduce the need for annual vaccinations with vaccines chosen upon predicting the predominant circulating viral strains, and to ameliorate the threat of cyclically occurring pandemics that have, in the past, killed tens of millions. Here, we describe a vaccine regimen based on sequential immunization with two serologically distinct chimpanzee-derived replication-defective adenovirus (Ad) vectors expressing the matrix-2 protein ectodomain (M2e) from three divergent strains of influenza A virus fused to the influenza virus nucleoprotein (NP) for induction of antibodies to M2e and virus-specific CD8(+) T cells to NP. In preclinical mouse models, the Ad vaccines expressing M2e and NP elicit robust NP-specific CD8(+) T-cell responses and moderate antibody responses to all three M2e sequences. Most importantly, vaccinated mice are protected against morbidity and mortality following challenge with high doses of different influenza virus strains. Protection requires both antibodies to M2e and cellular immune responses to NP.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
authors.forename: Te-Lang
authors.initials: TL
authors.lastname: Wu
authors.forename: Marcio O
authors.initials: MO
authors.lastname: Lasaro
authors.forename: Brian P
authors.initials: BP
authors.lastname: Latimer
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Parzych
authors.forename: Ang
authors.initials: A
authors.lastname: Bian
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Xiang
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D007252:Influenza Vaccines; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins