VRC01 HIV antibody falls short in trials, but don’t discount antibodies yet

An anti-HIV antibody called VRC01 does not protect people from acquiring HIV, according to findings from the Antibody-Mediated Prevention (AMP) Trials. 

The results were recently reported in the New England Journal of Medicine. While they indicate that this antibody alone is not a strong HIV-prevention measure, the data suggest that antibodies remain a potentially viable tactic for prevention. 

VRC01 initially was isolated by the National Institute of Allergy and Infectious Diseases (NIAID), then manufactured at the Frederick National Laboratory’s Vaccine Clinical Materials Program (VCMP) for the AMP Trials.  

“We are a small pilot plant facility, and to be able to support a relatively large international Phase II trial that will impact the future of HIV monoclonal antibody treatment is a major accomplishment for those who worked on this multiyear manufacturing campaign,” said Chris Case, Ph.D., manager of scientific programs at the VCMP, who was not involved with the trials. 

In total, the program produced more than 150,000 vials. The antibody has previously demonstrated effectiveness in preclinical models. 

The AMP Trials, a pair of studies—one conducted in the U.S., Switzerland, and South America, and one in sub-Saharan Africa—administered VRC01 to more than 4,600 people from certain groups at risk of acquiring HIV. Each participant received either a low dose, a high dose, or a control once every eight weeks for 20 months. (Participants were also offered an HIV-prevention medication, but many declined.) Doctors regularly monitored participants for HIV so that they could quickly receive antiretroviral therapy if they acquired the virus. 

VRC01’s overall efficacy at preventing HIV was less than 27% in both trials (although the high-dose group in one trial did have nearly 31% efficacy). This is well below what’s considered acceptable for vaccines and preventive medicines. 

Antibodies still have potential 

However, as part of the trial, scientists analyzed VRC01’s efficacy against different varieties of HIV in the laboratory, and something stood out. The antibody was approximately 75% effective against more sensitive versions of the virus. (It wasn’t effective against intermediate or resistant versions.) 

The 75% efficacy is still weaker than standard currently available preventive medications, but the scientists conducting the study view it as encouraging evidence of a larger picture. While VRC01 fails to prevent people from acquiring HIV most of the time, its majority effectiveness against sensitive versions demonstrates that antibodies themselves aren’t a futile endeavor. VRC01 can protect against certain varieties of HIV, just not most of them. 

As such, different antibodies may represent opportunities for protection against different types of the virus. This opens the door for engineering antibodies that could be more effective or more capable of protecting against different varieties of HIV. 

“The results are an important proof of concept that antibodies can be an effective preventative measure for HIV-1 acquisition. But in order for this treatment to be effective, the data suggest that ultimately you will need an antibody or antibody cocktail that covers a larger breadth of HIV-1 isolates than VRC01 alone,” Case said. 

More research is needed in these areas. Some studies are currently underway. 

The VCMP has used and is using its capabilities to help NIAID and its collaborators in this effort. The staff has manufactured seven other anti-HIV antibodies in the last five years, many of which have been deployed in clinical trials. 

“We anticipate that they will continue to develop new and improved antibodies to maximize the breadth of HIV-1 isolate coverage, and we look forward to generating the next class of anti-HIV antibodies to support them in their mission,” Case said. 

Beyond the efficacy data, the trials demonstrated that it’s possible to conduct long-term, logistically complex HIV clinical studies with thousands of participants spanning several countries, which paves the way for future trials. Additional findings also showed that a certain biological measurement taken from participants’ blood serum could predict protection, representing a potentially useful method for future analyses. 

Much work remains to be done on antibodies as an HIV-prevention technique, but the book hasn’t closed on them yet. 

Image by NIAID, reproduced here under a CC BY 2.0 license