Broadly Neutralizing Antibodies against HIV: Back to Blood. Issue 3 (March 2019)

• Record Type: Journal Article
• Authors: Dashti, Amir; DeVico, Anthony L.; Lewis, George K.; Sajadi, Mohammad M.
• Is Part Of: Trends in molecular medicine. Volume 25:Issue 3(2019)
• Page Start: 228
• Page End: 240
• Publication Date: 2019-03
• Subjects: antibody -- bNAbs -- gp120 -- HIV -- neutralization -- vaccine; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2019.01.007
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : After years of continuous exposure to HIV envelope antigens, a minority of HIV-infected individuals develop a cognate polyclonal humoral response comprising very potent and extremely cross-reactive neutralizing antibodies [broadly neutralizing antibodies (bNAbs)]. Isolated bNAbs derived from memory B cell pools have been the focus of intense studies over the past decade. However, it is not yet known how to translate the features of bNAbs into practical HIV prevention methods. In this review, we attempt to seek insights from emerging information about the human broadly neutralizing plasma response as well as its frequency, clonal composition, specificity, potency, and commonality among infected subjects. We also consider how this information points to selecting and prioritizing certain epitope targets and strategies for HIV vaccine design. Highlights: A minority of HIV-infected subjects develop plasma-neutralizing responses with near-pan-neutralization breadth against heterologous virus strains. The development of such responses, depending on epitope specificity, is linked to infecting clade, viral load, duration of infection, and virus and host genetic factors. New approaches allow extremely broad and potent bNAbs to be derived directly from human plasma responses. In some cases, broadly neutralizing plasma activity traces to a single lineage of a few related bNAbs, representing a minority of the polyclonal anti-HIV envelope response. The cocirculation of poorly neutralizing/non-neutralizing antienvelope antibodies does not abrogate the persistence and activities of the bNAbs. Each class of known bNAb exhibits at least one 'atypical' trait (e.g., high somatic hypermutation, long HCDR3, and/or auto/polyreactivity). Among bNAbs types, those against the CD4bs are seen more frequently, share common features among diverse subjects, and exhibit extreme neutralization breadth and potency.