title: Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.
abstract: Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Jaworski
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Bryk
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Brower
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Hessell
authors.affiliation: Divsion of Allergy, Immunology & Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Rosenberg
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Tong Tong
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Lowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sanz
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Haigwood
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: James J
authors.identifier: http://orcid.org/0000-0001-8069-0272
authors.initials: JJ
authors.lastname: Kobie
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D016175:B-Lymphocyte Subsets; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015686:Gene Products, env / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D007074:Immunoglobulin G