Broadly neutralizing antibodies for treatment and prevention of HIV-1 infection

Abstract

Purpose of reviewAnti-HIV-1 broadly neutralizing antibodies (bNAbs) are promising agents in the fight against the AIDS epidemic. Multiple bNAbs have been already evaluated in clinical trials with encouraging results. This review discusses the use of bNAbs for the prevention and treatment of HIV-1 infection, focusing on manufactured products that have been evaluated in clinical settings. Recent findingsMore than 17 bNAbs have been evaluated for safety and pharmacokinetics in humans. The vast majority presented a well tolerated profile and were generally well tolerated. Serum half-life varied from 12 to 73.5 days and can be improved by the addition of mutations to the Fc regions. Results from the antibodymediated prevention (AMP) study show that VRC01, a CD4-binding-site bNAb, was effective at preventing the acquisition of sensitive HIV-1 strains but did not prevent the acquisition of strains whose in vitro sensitivity to the antibody had an IC 80 of more than 1 mg/ml. New bNAb combinations to improve coverage are currently being evaluated.

Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana

“…A randomized design comparing bNAbs with an analytic treatment interruption (ATI) was not considered feasible at the time Tatelo was conducted, but for children with low or undetectable reservoirs and a constellation of favorable markers, an ATI component could be considered in future trials. Given the potential vaccinal effect ( 16 , 17 ) and reservoir-lowering effect ( 1 , 4 , 18 , 19 ) previously described for bNAbs, candidates for such a trial may benefit from a period of bNAbs before ATI to maximize the chance for success.…”

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition

“…K d and Q max were calculated by the Scatchard equation as 0.3 ± 0.014 nmol/g and 36.7 ± 2.2 nM, respectively (Figure S7), showing a comparable affinity level to the bnAbs against HIV-1 Env (10−100 nM). 6,44 Finally, the dynamic adsorption curves of GINPs and NINPs on HIV-1 were explored with an adsorption equilibrium of approximately 20 min (Figure 2F), displaying swift binding kinetics.…”

“…Therefore, the virus can easily evade the host immune system, which also weakens the efficacy of vaccines in eliciting neutralizing antibody responses to combat the virus. Although vaccines are widely acknowledged as one of the most effective ways to prevent AIDS, the presence of a glycan shield on the envelope (Env) of HIV-1 brings significant challenge to the vaccine development. , Other prophylactic and therapeutic methods have also been developed, such as broadly neutralizing antibodies (bnAbs) − and antiretroviral drugs. − Nevertheless, drug resistance and the rapidly changing viral antigenic profile pose significant challenges and place greater demands on the timeliness of drug and vaccine development.…”

Broadly neutralizing antibodies for HIV treatment and cure approaches

“…Longitudinal studies show that anti-HIV antibodies from elite neutralizers increase in breadth and potency over time [6]. Among the hundreds of isolated bNAb candidates, 18 are currently investigated in registered clinical trials [7–14,15 ▪ ,16–24] (summarized in Table 1). All these bNAbs bind to different regions of the viral envelope glycoprotein Env.…”