Novel hemagglutinin nanoparticle influenza vaccine with Matrix-M™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted A(H3N2) subtypes
Autor: | Ye Liu, Bin Zhou, Nita Patel, Gale Smith, Larry Ellingsworth, Michael J. Massare, Maggie Lewis, James F. Cummings, David Flyer, Greg Glenn |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Influenza vaccine Hemagglutinin (influenza) Biology Antibodies Viral Virus Epitope Antigenic drift Microbiology Mice 03 medical and health sciences Influenza A Virus H1N1 Subtype Animals Hemagglutination assay General Veterinary General Immunology and Microbiology Influenza A Virus H3N2 Subtype Ferrets Public Health Environmental and Occupational Health virus diseases Hemagglutination Inhibition Tests Antibodies Neutralizing Virology Hemagglutinins 030104 developmental biology Infectious Diseases Influenza Vaccines Viral evolution biology.protein Nanoparticles Molecular Medicine Antibody |
Zdroj: | Vaccine. 35:5366-5372 |
ISSN: | 0264-410X 2000-2017 |
Popis: | Influenza viruses frequently acquire mutations undergoing antigenic drift necessitating annual evaluation of vaccine strains. Highly conserved epitopes have been identified in the hemagglutinin (HA) head and stem regions, however, current influenza vaccines induce only limited responses to these conserved sites. Here, we describe a novel seasonal recombinant HA nanoparticle influenza vaccine (NIV) formulated with a saponin-based adjuvant, Matrix-M™. NIV induced hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies against a broad range of influenza A(H3N2) subtypes. In a comparison of NIV against standard-dose and high-dose inactivated influenza vaccines (IIV and IIV-HD, respectively) in ferrets NIV elicited HAI and MN responses exceeding those induced by IIV-HD against homologous A(H3N2) by 7 fold, A(H1N1) by 26 fold, and B strain viruses by 2 fold. NIV also induced MN responses against all historic A/H3N2 strains tested, spanning more than a decade of viral evolution from the 2000-2017 influenza seasons whereas IIV and IIV-HD induced HAI and MN responses were largely directed against the homologous A(H3N2), A(H1N1), and B virus strains. NIV induced superior protection compared to IIV and IIV-HD in ferrets challenged with a homologous or 10-year drifted influenza A(H3N2) strain. HAI positive and HAI negative neutralizing monoclonal antibodies derived from mice immunized with NIV were active against homologous and drifted influenza A(H3N2) strains. Taken together these observations suggest that NIV can induce responses to one or more highly conserved HA head and stem epitopes and result in highly neutralizing antibodies against both homologous and drift strains. |
Databáze: | OpenAIRE |
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