title: B Cell Responses Associated with Vaccine-Induced Delayed SIVmac251 Acquisition in Female Rhesus Macaques.
abstract: An established sex bias in HIV pathogenesis is linked to immune responses. Recently we reported a vaccine-induced sex bias: vaccinated female but not male rhesus macaques exhibited delayed SIV acquisition. This outcome was correlated with SIV Env-specific rectal IgA, rectal memory B cells, and total rectal plasma cells. To uncover additional contributing factors, using samples from the same study, we investigated memory B cell population dynamics in blood, bone marrow, and rectal tissue during immunization and postchallenge; IgG subtypes and Ab avidity; and regulatory B (Breg) cell frequency and function. Few sex differences were seen in Env-specific memory B cell, plasmablast, or plasma cell frequencies in the three compartments. Males had higher IgG Ab titers and avidity indices than females. However, females had elevated levels of Env-specific IgG1, IgG2, and IgG3 Abs compared with males. gp140-specific IgG3 Abs of females but not males were correlated with Ab-dependent cell-mediated cytotoxicity activity against gp120 targets (p = 0.026) and with Ab-dependent phagocytic activity (p = 0.010). IgG3 Ab of females but not males also correlated with decreased peak viremia (p = 0.028). Peripheral blood CD19(+)CD25(+) Breg cells suppressed T cell proliferation compared with CD19(+)CD25(-) cells (p = 0.031) and exhibited increased IL-10 mRNA expression (p = 0.031). Male macaques postvaccination (p = 0.018) and postinfection (p = 0.0048) exhibited higher Breg frequencies than females. Moreover, male Breg frequencies correlated with peak viremia (p = 0.0071). Our data suggest that vaccinated females developed better Ab quality, contributing to better functionality. The elevated Breg frequencies in males may have facilitated SIV acquisition.
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Venkatramanan
authors.identifier: 0000-0002-8221-5982
authors.initials: V
authors.lastname: Mohanram
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Demberg
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Musich
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Iskra
authors.initials: I
authors.lastname: Tuero
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Diego A
authors.identifier: 0000-0001-7405-9572
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Leia
authors.initials: L
authors.lastname: Miller-Novak
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892.
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.affiliation: Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and guroffm@mail.nih.gov.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D010587:Phagocytosis; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D014766:Viremia / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D016753:Interleukin-10