Four innovative studies investigating broadly neutralizing antibodies (bNAbs) have been awarded research grants totaling nearly $3 million, by amfAR, The Foundation for AIDS Research. These hypermutated antibodies can penetrate components of HIV that are less likely to change genetically, giving bNAbs the potential to target a broad range of HIV strains.

It’s believed that these specific types of antibodies, which a small percentage of people living with HIV produce naturally, albeit after many years, could be administered as an infusion to neutralize HIV and make it harmless. That’s why researchers have cautious early optimism about the potential for bNAbs to prevent and cure HIV. An HIV cure has been so elusive because of the virus’s ability to easily mutate, and because viral reservoirs develop early in the acquisition of HIV. In theory, the body’s natural immune system could use bNAbs to create antibodies that prevent HIV from binding to T cells. Using the body’s immune system with engineered components is still highly experimental, but over the past decade, there has been rising enthusiasm in the HIV research community about its potential.

“amfAR thinks there is a role for bNAbs as an important part of a cure strategy, but right now there is not enough information about how long they work,” amfAR senior scientific consultant Dr. Jeffrey Laurence said.

This round of amfAR grants includes:

Research from the University of California, San Francisco (UCSF), to analyze data from five clinical trials to understand why, in some of the trials, administering a cocktail of bNAbs at the point of stopping antiretroviral therapy (ART) improves control of HIV. Several cure studies have shown that, even though HIV eventually rebounds, using bNAbs at the point of treatment interruption prolongs the period of post-treatment viral control. Rachel Rutishauser, MD, PhD, of UCSF, and a team of investigators from the U.S. and Denmark will explore mechanisms that mediate this control. The team will compare specific immune responses in more than 100 study participants to test the hypothesis that an infusion of bNAbs at the point of treatment interruption leads to boosting the immune response in some people. “This research will explore whether the (immune response) is souped-up T cell immunity or something else,” Laurence said.

A second amfAR grant will go to James M. Termini, PhD, of the University of Miami, to determine why, in the absence of antiretrovirals in animal models, anti-HIV bNAbs have not been able to eradicate HIV reservoirs. The persistence of viral reservoirs has been a huge, persistent roadblock to developing a cure for HIV.

That viral reservoir is the subject of a third grant, awarded to Mary Ann Checkley-Luttge, PhD, of Case Western Reserve University, who will test two types of genetically-engineered natural killer cells, or iNK cells, to determine whether they reduce the HIV reservoir. Dr. Checkley-Luttge and her team will combine iNK cells with bNAbs in test tube studies to study how potent they may be against HIV reservoirs—if they see a 50% reduction in intact HIV reservoir virus from cells taken from six people living with HIV, they may progress to animal and human studies, according to amfAR.

Finally, a team headed by Xu Yu, MD, of Massachusetts General Hospital, will receive supplemental funding for ongoing research to determine whether some people on antiretroviral therapy have cleared their bodies of HIV without realizing it. The team has followed 66 individuals on ART for at least 15 years. The additional funding will allow researchers to observe what happens when ART is interrupted among the 66 and see if immune selection against HIV reservoirs could lead to them being cured.

In addition to these four, amfAR funded 23 other HIV cure research teams in 2023, according to Laurence. He adds that bNAbs hold promise for a cure, but there are many questions to be answered. “For one, we know that if you treat a monkey with antiretrovirals plus bNAbs, it can go a long time without relapsing, but we don’t know how long. Another question is, can you use antibodies that are not broadly acting but equally effective?”

Laurence notes that research into bNAbs could be applied to other common viruses with latent periods, including Epstein-Barr, herpes and SARS CoV-2.   

Larry Buhl is a multimedia journalist based in Los Angeles. He has covered HIV/AIDS and other infectious diseases for more than two decades. In addition to POSITIVELY AWARE, he is a regular contributor to, Everyday Health and His work has appeared in USA Today, Salon, Undark, KQED, the New York Times and others.