Antibody-mediated prevention and treatment of HIV-1 infection

Abstract

Novel broadly neutralizing antibodies targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation. These include the use of antibody combinations to prevent viral escape, antibody modifications to increase the half-life and the co-administration of latency-reversing agents to target the cellular reservoir of HIV-1. We provide an overview of the results of pre-clinical and clinical studies of broadly HIV-1 neutralizing antibodies, discuss their implications and highlight approaches for the ongoing advancement into humans.

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody

“…Although these results highlight the significant clinical potential of bNAbs, pre-existing or de novo HIV-1 resistance cause treatment failure and can strongly limit bNAb applications in humans (Bar et al, 2016; Bar-On et al, 2018;Caskey et al, 2015Caskey et al, , 2017Lynch et al, 2015a;Mendoza et al, 2018;Scheid et al, 2016). Strategies to prevent and overcome viral escape are therefore critical to effectively implement bNAb-mediated approaches for HIV-1 prevention and therapy (Caskey et al, 2019;Gruell and Klein, 2018).…”

Anti‐HIV‐1 antibodies trigger non‐lytic complement deposition on infected cells

“…Env exists in at least two conformations, a native "close" configuration and a CD4-bound "open" conformation (reviewed in [11]). In animal models, infusion of bNAbs protects against HIV-1 acquisition, decreases viral load [14,15], modulates host immune responses [16,17], and, when associated to latency-reversal agents, delays viral rebound after treatment interruption [18,19]. These antibodies target the CD4 binding site (CD4bs), the N-glycans of V1/V2 and V3 loops, the gp41 membrane proximal external region (MPER), and the gp120/gp41 interface [12].…”

“…These antibodies target the CD4 binding site (CD4bs), the N-glycans of V1/V2 and V3 loops, the gp41 membrane proximal external region (MPER), and the gp120/gp41 interface [12]. In animal models, infusion of bNAbs protects against HIV-1 acquisition, decreases viral load [14,15], modulates host immune responses [16,17], and, when associated to latency-reversal agents, delays viral rebound after treatment interruption [18,19]. At least nine bNAbs are currently under clinical evaluation, either alone or in combination, and display antiviral activity in humans [20].…”

Blood-borne disease markers analysis, creating testing algorithms and application of preventive measures

“…Značajno je istaći da ne postoje dokazi da se HIV razmnožava u bilo kojoj vrsti zglavkara; 3. zdravstveni radnici mogu biti u povećanom riziku samo ukoliko se ne pridržavaju osnovnih i specijalnih mera zaštite i prevencije, Poznavanje epidemiologije i puteva prenošenja HIV-a određuje mere prevencije. Iako se ulažu veliki napori u iznalaženju vakcine protiv AIDS-a, do danas je, zbog kompleksnosti virusa, sve ostalo na eksperimentom nivou [33][34][35][36][37][38][39][40][41][42][43].…”