title: Impact of preexisting memory to seasonal A/H1N1 influenza virus on the immune response following vaccination against avian A/H5N1 virus.
abstract: Cross-protection against divergent strains of influenza virus is an objective of various vaccination approaches. B cells cross-neutralizing several influenza A heterosubtypes have been isolated from cultured human memory B cells (MBCs) and plasmablasts early after influenza vaccination or infection. However, a systematic assessment of the frequency of MBCs and plasmablasts in the blood of healthy individuals is lacking. Here, we show that under resting conditions about 45% of human adults never vaccinated nor exposed to avian A/H5N1 influenza have detectable circulating MBCs cross-reacting with H5N1. This proportion rises to 63.3% among subjects with a large pool of MBCs specific for seasonal H1N1 (i.e. frequency ≥1% of total IgG MBCs). Moreover, subjects with high baseline frequencies of H1N1-specific MBCs had an expansion of H5N1-specific MBCs producing H5-neutralizing antibodies already after the first dose of an MF59-adjuvanted H5N1 vaccine. These results suggest that H1N1-specific MBCs contain a subset of cells cross-reacting to H5. We propose that a proportion of human adults have a pool of H5/H1 cross-reactive MBCs that contribute to the rapid rise of the antibody response to divergent influenza strains. This may have implications on vaccination strategies aimed at counteracting future influenza pandemics.
authors.affiliation: Research, Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buricchi
authors.forename: Monia
authors.initials: M
authors.lastname: Bardelli
authors.forename: Carmine
authors.initials: C
authors.lastname: Malzone
authors.forename: Barbara
authors.initials: B
authors.lastname: Capecchi
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.forename: Elena
authors.initials: E
authors.lastname: Fragapane
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Grazia
authors.initials: G
authors.lastname: Galli
authors.forename: Oretta
authors.initials: O
authors.lastname: Finco
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines