title: Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies.
abstract: Induction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV-1) is a key, as-yet-unachieved goal of prophylactic HIV-1 vaccine strategies. However, some HIV-infected individuals develop bnAbs after approximately 2-4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+(Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy-chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV-1 infection, in particular alterations in CD4+Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV-1 vaccine design.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.affiliation: Duke University Human Vaccine Institute and Departments of Pediatrics and Immunology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D018858:Germinal Center / Q000276:immunology*; D015483:HIV Antibodies / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007156:Immunologic Memory; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: CD4+ T follicular helper cell; CD4+ T follicular regulatory cell; autoantibody; broadly neutralizing antibody; human immunodeficiency virus; regulatory T cell