Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity

Purpose of reviewTreatment with combinations of complementary broadly neutralizing antibodies (bnAbs) has increased the proportion of participants for whom bnAbs can maintain virus suppression upon cessation of antiretroviral therapy (ART). There remains, however, a population of trial participants who experience virus rebound despite high plasma concentrations of bnAbs. Thus, baseline resistance remains a critical barrier to the efficacy of bnAbs for use in the treatment and cure of HIV, and the development of a screening assay to guide bnAb selection is a high priority.Recent findingsThere are two conceptual approaches to assess the putative rebound-competent HIV-1 reservoir for bnAb sensitivity: to assess neutralization sensitivity of reactivated virus in outgrowth assays and sequence-based approaches that include a selection for intact genomes and assessment of known resistance mutations within the env gene. Currently, the only phenotypic assay for bnAb screening that is clinical laboratory improvement amendments certified (CLIA certified) and available for clinical trial use is Monogram Biosciences’ PhenoSense HIV Neutralizing Antibody Assay.SummarySeveral new approaches for screening are currently under development and future screening methods must address three issues. First, complete sampling of the reservoir may be impossible, and determination of the relevance of partial sampling is needed. Second, multiple lines of evidence indicate that in vitro neutralization measures are at least one correlate of in vivo bnAb activity that should be included in screening, but more research is needed on how to use in vitro neutralization assays and other measures of antibody functions and measures of other antibody features. Third, the feasibility of screening assays must be a priority. A feasible, predictive bnAb screening assay will remain relevant until a time when bnAb combinations are substantially more broad and potent.

Section: The Phenosense Assaymentioning

confidence: 99%

Section: The Phenosense Assaymentioning

confidence: 99%

Development of screening assays for use of broadly neutralizing antibodies in people with HIV

Lynch

Bar

2023

“…More recently, two other studies have also reported the effect of anti-HIV-1 bNAbs on the stimulation of T-cell immunity. Rosas-Umbert et al [32 ▪▪ ] showed that administration of HIV-1 bNAbs at the initiation of ART maintained long-term CD8 + T-cell immunity. They observed that the frequency of Pol and Gag specific CD8 + T cells, as well as Gag induced interferon-γ responses, were significantly higher in patients who received adjuvant 3BNC117 therapy than in those who received ART alone.…”

Section: Vaccinal Effect Of Antiviral Monoclonal Antibodies: From Pre...mentioning

confidence: 99%

“…Different clinical trials have now shown the immune-enhancing effect of bNAbs, through the potentiation of the humoral [30] and cellular immune response [31,32 ▪▪ ,33 ▪▪ ]. However, the induction of vaccinal effects is not systematic, as it has not been observed in other clinical trials performed with the same bNAbs [34,35].…”

Section: How Can the Vaccinal Effect Be Improved?mentioning

confidence: 99%

Vaccinal effect of HIV-1 antibody therapy: dream or reality?

Naranjo-Gómez

Pelegrin

2023

Purpose of reviewThis review summarizes recent studies reporting the induction of vaccinal effects by human immunodeficiency virus (HIV-1) antibody therapy. It also puts into perspective preclinical studies that have identified mechanisms involved in the immunomodulatory properties of antiviral antibodies. Finally, it discusses potential therapeutic interventions to enhance host adaptive immune responses in people living with HIV (PLWH) treated with broadly neutralizing antibodies (bNAbs).Recent findingsRecent studies in promising clinical trials have shown that, in addition to controlling viremia, anti-HIV-1 bNAbs are able to enhance the host's humoral and cellular immune response. Such vaccinal effects, in particular the induction of HIV-1-specific CD8+ T-cell responses, have been observed upon treatment with two potent bNAbs (3BNC117 and 10–1074) alone or in combination with latency-reversing agents (LRA). While these studies reinforce the idea that bNAbs can induce protective immunity, the induction of vaccinal effects is not systematic and might depend on both the virological status of the patient as well as the therapeutic strategy chosen.SummaryHIV-1 bNAbs can enhance adaptive host immune responses in PLWH. The challenge now is to exploit these immunomodulatory properties to design optimized therapeutic interventions to promote and enhance the induction of protective immunity against HIV-1 infection during bNAbs therapy.

“…Infusion of bNAbs can prevent HIV-1 infection of naïve individuals and suppress viral replication in those already infected, provided that the virus is sensitive [2–4]. An increasing body of evidence is suggesting that bNAbs add to existing ART, by providing long-lasting protection, by targeting the viral reservoir and potentially by stimulating endogenous immune responses [5 ▪▪ ,6,7 ▪▪ ,8].…”

Section: Introductionmentioning

confidence: 99%

Polyfunctionality of broadly neutralizing HIV-1 antibodies

Vrignaud,

Schwartz,

Bruel

2023

Purpose of reviewThe discovery of broadly neutralizing HIV-1 antibodies (bNAbs) has provided a framework for vaccine design and created new hope toward an HIV-1 cure. These antibodies recognize the HIV-1 Envelope and inhibit viral fusion with unprecedented breadth and potency. Beyond their unique neutralization capacity, bNAbs also activate immune cells and interfere with viral spread through nonneutralizing activities. Here, we review the landscape of bNAbs functions and their contribution to clinical efficacy. Recent findingsParallel evaluation of bNAbs nonneutralizing activities using in vivo and in vitro models have revealed how their importance varies across antibodies and strains. Nonneutralizing bNAbs functions target both infected cells and viral particles, leading to their destruction through various mechanisms. Reservoir targeting and prevention in context of suboptimal neutralization highly depends on bNAbs polyfunctionality. We recently showed that bNAbs tether virions at the surface of infected cells, impairing release and forming immune complexes, with consequences that are still to be understood.