Neutralizing Antibodies May Provide a New Approach to Longstanding Infections

Everyone has neutralizing antibodies (NAbs).

NAbs defend our cells against pathogens by diminishing their infectivity. While binding antibodies attach to a pathogen and activate immune cells to destroy it, NAbs simply inhibit the pathogen’s biological effect.

Scientists use NAbs in both active and passive immunization. Vaccines are the most common active immunization example. Serum therapy is a passive immunization treatment that involves administering a recovered patient’s blood serum to an infected patient. Recently, investigators have been studying NAb-based therapies to treat and prevent COVID-19.

Most NAbs are very specific for one pathogen. Consequently, pathogens that frequently mutate, like HIV, pose a challenge. However, broadly neutralizing antibodies (bNAbs) are a potential solution that can inactive multiple strains of a virus. Currently, investigators have found bNAbs for HIV, hepatitis C, and influenza, among others.

A study published in March 2021 in The New England Journal of Medicine investigated if a bNAb (VRC01) can prevent HIV-1 infection. One trial enrolled 2699 at-risk cisgender men and transgender individuals in the Americas and Europe, and a second trial enrolled at-risk women in sub-Saharan Africa. Investigators randomized patients to receive either:

• 10 mg per kg VRCO1 infusion (low dose)
• 30 mg per kg VRC01 infusion (high dose)
• Placebo

The investigators looked at 2 things: acquisition and prophylaxis of infection. Participants received 10 infusions in total and underwent HIV-1 testing every 4 weeks. The results concluded that VRC01 did not prevent HIV-1 acquisition. However, VRC01-sensitive HIV-1 isolate analyses suggest bnAb prophylaxis can be effective. The investigators assert that virus strain’s susceptibility to VRC01 was an important factor in antiviral activity. VRC01 only effectively inhibited 30% of the virus strains in the trial regions but provided 75% protection in participants with VRC01-sensitive strains.

While VRC01 did not prevent HIV-1 acquisition, the study demonstrated that preventing HIV infection with bNAbs is feasible. Researchers are currently conducting early phase clinical trials on various bnAbs, including combination products. If these new bnAbs are effective, they can be used to prevent HIV infections and save countless of lives.

Alexandra Bieniek is a 2022 PharmD candidate at the University of Connecticut in Storrs.

REFERENCE

Corey L, Gilbert PB, Juraska M, et al. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021;384(11):1003-1014. doi:10.1056/NEJMoa2031738