title: HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation.
abstract: Infection with HIV drives significant alterations in B cell phenotype and function that can markedly influence antibody responses to immunisation. Anti-retroviral therapy (ART) can partially reverse many aspects of B cell dysregulation, however complete normalisation of vaccine responsiveness is not always observed. Here we examine the effects of underlying HIV infection upon humoral immunity to seasonal influenza vaccines. Serological and memory B cell responses were assessed in 26 HIV+ subjects receiving ART and 30 healthy controls immunised with the 2015 Southern Hemisphere trivalent inactivated influenza vaccine (IIV3). Frequencies and phenotypes of influenza hemagglutinin (HA)-specific B cells were assessed by flow cytometry using recombinant HA probes. Serum antibody was measured using hemagglutination inhibition assays. Serological responses to IIV3 were comparable between HIV+ and HIV- subjects. Likewise, the activation and expansion of memory B cell populations specific for vaccine-component influenza strains was observed in both cohorts, however peak frequencies were diminished in HIV+ subjects compared to uninfected controls. Lower circulating frequencies of memory B cells recognising vaccine-component and historical influenza strains were observed in HIV+ subjects at baseline, that were generally restored to levels comparable with HIV- controls post-vaccination. HIV infection is therefore associated with depletion of selected HA-specific memory B cell pools.
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Wheatley
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Kristensen
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: William N
authors.initials: WN
authors.lastname: Lay
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia.|Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D018655:Lymphocyte Count; D012621:Seasons; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines