title: Improved adjuvanting of seasonal influenza vaccines: preclinical studies of MVA-NP+M1 coadministration with inactivated influenza vaccine.
abstract: Licensed seasonal influenza vaccines induce antibody (Ab) responses against influenza hemagglutinin (HA) that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia Ankara (MVA) virus encoding NP and M1 (MVA-NP+M1) is designed to boost preexisting T-cell responses in adults in order to elicit a cross-protective immune response. We examined the coadministration of HA protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Ab responses postimmunization were measured by ELISA and pseudotype neutralization assays. Here, we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing Ab responses to HA while simultaneously inducing potent T-cell responses to conserved internal Ags. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and Ab responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations.
authors.affiliation: Jenner Institute, Old Road Campus Research Building, Oxford, UK. caitlin.mullarkey@ndm.ox.ac.uk
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Mullarkey
authors.forename: Amy
authors.initials: A
authors.lastname: Boyd
authors.forename: Arjan
authors.initials: A
authors.lastname: van Laarhoven
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lefevre
authors.forename: B
authors.initials: B
authors.lastname: Veronica Carr
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Baratelli
authors.forename: Eleonora
authors.initials: E
authors.lastname: Molesti
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Temperton
authors.forename: Colin
authors.initials: C
authors.lastname: Butter
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
authors.forename: Teresa
authors.initials: T
authors.lastname: Lambe
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001717:Birds; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology; D034421:Sus scrofa; D013552:Swine; D019444:Vaccines, DNA; D014758:Viral Core Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C560489:MVA vaccine; D009698:Nucleoproteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014765:Viral Vaccines
keywords: Adjuvants; Influenza vaccines; T cells; Vaccination