title: Immune System Regulation in the Induction of Broadly Neutralizing HIV-1 Antibodies.
abstract: In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of HIV-1 are weakly immunogenic because they mimic host antigens. In consequence, B cells that strongly bind these determinants are removed by the physiological process of immune tolerance. This structural mimicry may represent a significant impediment to designing protective HIV-1 vaccines, but we note that several vaccine strategies may be able to mitigate this evolutionary adaptation of HIV and other microbial pathogens.
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA ; The Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: The Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA ; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Verkoczy
authors.affiliation: Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA ; The Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA ; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
keywords: B-cell lineage design; HIV-1 vaccine strategy; HIV-1 vaccines; broadly neutralizing antibody; immune tolerance