Abstract
Anti-human immunodeficiency virus type-1 (anti-HIV-1) neutralizing monoclonal antibodies are broadening the spectrum of pre- and post-exposure treatment against HIV-1. A better understanding of how these antibodies develop and interact with particular regions of the viral envelope protein is guiding a more rational structure-based immunogen design. The aim of this article is to review the most recent advances in the field, from the development of these particular antibodies during natural HIV-1 infection, to their role preventing infection, boosting endogenous immune responses and clearing both free viral particles and persistently infected cells.
Highlights
Reviewed by: Christiane Moog, French Institute of Health and Medical Research, France Marjorie Robert-Guroff, National Cancer Institute, USA
Considering that virus suppression failed in patients with resistant viral variants, these results suggest that immunotherapy will require the combination of multiple broad NmAbs (bNmAbs) that target different sites on HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) envelope proteins (Env) for clinical use
The continued pursuit of comprehensive studies of bNmAb structures and their interaction with HIV-Env and further investigations into the mechanisms involved in B-cell development and maturity that lead to the expansion of bNmAbs, constitute the basis for the rational design of novel immunogens to be included in an effective HIV-1 vaccine
Summary
CD4-binding site (conformational epitope) b12d [18] VRC01 (01–03) [47] VRC07 [61] 3BNC117 [55, 60, 117] [44] NIH45-46 [44] G54W 12A12 [44] VRCPG04 [48, 142] VRC-CH31 [30,31,32,33,34] [48] HJ16 [54] N6. Using the NHP/SHIV model, two separate studies showed that a single administration of new generation bNmAbs to chronically infected macaques reduced viremia and cellassociated viral loads—in peripheral blood, gut mucosa, and lymph nodes—to undetectable levels for a period of 3–8 weeks [73, 74] In these studies, effective virus control was positively correlated with bNmAbs potency and half-life. The positive outcomes observed in NHP and hu-mouse models prompted the testing of new generation bNmAbs in HIV-1 chronically infected patients In this regard, two separate studies showed that the administration of a single dose of 3BNC117 or VRC01 reduced HIV-1 viremia (from 1 to 2.5 log10) for as long as 1 month, in patients who were not under combination antiretroviral treatment (cART) [75, 76]. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs
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