UPDATED: IAVI Sees Hope in Findings of Antibody-Mediated Prevention Study

IAVI congratulates the U.S. National Institutes of Health (NIH) and the HIV Vaccines Trial Network (HVTN) on the successful conduct of the Antibody-Mediated Prevention (AMP) study and commends the contributions the trial participants made toward answering essential scientific questions. In the trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) researchers investigated whether participants who received repeated intravenous infusions of the NIH-discovered and developed VRC01 antibody were protected from HIV infection. Early findings from the study were shared at the HIV Research for Prevention (HIVR4P) Conference, and the results were published the following month in the New England Journal of Medicine (NEJM).

Drawing up fluid when preparing an for intravenous infusion. Courtesy of the U.S. National Library of Medicine, Bethesda, Maryland

Preclinical research had indicated that VRC01 neutralized up to 90% of a globally representative sample of 200 HIV strains using pseudoviruses in an in vitro assay. Such broad protection from HIV isolates was not seen in this clinical study, however, due to the neutralization resistance to VRC01 by the majority of viruses that actually infected participants in the study. A subanalysis suggests that trial participants who were exposed to viruses that were highly sensitive to VRC01 were at much less risk for HIV infection compared to those who did not receive the antibody.

The ability to make meaningful interpretations of this milestone study in all of its nuances is attributable to a carefully crafted clinical design by leaders of the HVTN/HPTN network as well as leading investigators tasked with virology assessment, statistical analyses, and, of course, all of the clinical trial participants and organizers who made the landmark study possible.

Participants in HVTN 704/HPTN 085 were cisgender men and transgender individuals in the U.S. and Europe who have sex with men. The second AMP study (HVTN 703/HPTN 081) was conducted in sub-Saharan Africa; participants were cisgender women.

Mark Feinberg, M.D., Ph.D., president and CEO of IAVI said, “All of us in the HIV prevention field have been looking forward to learning results of this key proof-of-concept trial, and we see promise in the information presented today. Since the AMP study was launched in 2016, researchers, including IAVI and partner scientists, have been exploring how to identify and combine antibodies that will block a wider range of HIV variants. We have been making tremendous strides in engineering and optimizing HIV antibodies to be more potent and longer lasting. The AMP data encourage us to continue investigation of HIV broadly neutralizing antibodies (bnAbs) that are highly potent and broadly effective at neutralizing a range of HIV variants and advance their addition to the HIV prevention toolbox.”

Feinberg also noted the importance of the AMP study findings for the holy grail of HIV prevention: an HIV vaccine. The hunt for a vaccine has, for the past several years and among many researchers, shifted to the goal of eliciting broadly neutralizing antibodies through vaccination. Feinberg said, “Not only do the findings from the AMP study answer a fundamental question about whether a broadly neutralizing antibody can prevent HIV infection, they also provide important direction for HIV vaccine research: we now have confirmation that it makes sense to continue to develop vaccine candidates that aim to elicit broadly neutralizing antibodies. What’s more, we know what levels of circulating antibodies a vaccine would need to elicit for effective protection from HIV infection. Having this benchmark in mind will be a useful tool as we design and evaluate HIV vaccine candidates.”

Earlier this year, IAVI announced collaborations with Scripps Research, NIH, and Serum Institute of India Pvt. Ltd. (Serum Institute) with the goal of expediting the development of a combination of next-generation bnAbs for HIV prevention. IAVI will license optimized bnAbs targeting the CD4 binding site on the HIV Envelope surface glycoprotein developed by scientists at the NIAID Vaccine Research Center (VRC) and other NIAID laboratories. Via the partners’ joined efforts, and building on IAVI work enabled by generous and long-term investments made by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID), these highly promising bnAbs targeting distinct weaknesses on HIV will be optimized for potency, breadth, and manufacturability and for the most desirable product profile to foster ease of implementation and acceptance.

As the manufacturing partner, Serum Institute has a proven track record of more than 50 years in developing affordable medicines, including monoclonal antibody products. The partnership between IAVI and Serum Institute will focus on developing large-scale, low-cost manufacturing processes to produce optimized combinations of HIV antibodies. These combinations will be rigorously compared in preclinical and clinical trials to determine which combination is optimal for HIV prevention and potentially for treatment, and, if effective, registered and commercialized globally. IAVI and Serum Institute will simultaneously define a pathway for sustainable access and delivery of these antibodies in developing countries, in collaboration with other stakeholders.

These partnerships represent a unique collaboration framework in biomedical innovation, in which nonprofit, commercial, and governmental partners work to lower costs and enable delivery of a new HIV prevention product with the potential to profoundly change the trajectory of the HIV pandemic.

Now that AMP results have shown proof of concept, it is essential to develop bnAb combinations of optimal potency and breadth to bring to licensure and global access as quickly as possible. And it will be essential to create new pathways to enable promising bnAb combination products to be produced at sufficient scale to meet global needs and at a price that ensures availability and affordability to all who can benefit from them, especially people at risk of HIV in low-income countries. However, given that existing monoclonal antibody products targeting other diseases are available mainly in higher income countries at high prices, achieving this goal will require innovative science and innovative partnerships.

IAVI has recently published a global call to action highlighting the steps that global health stakeholders must take to ensure that monoclonal antibodies for a range of noncommunicable and infectious diseases, including HIV/AIDS and COVID-19, are widely available and accessible.

Feinberg said, “We look forward to working with the global health community to ensure that the combination products we’re developing, should they be shown to be efficacious, will be made available promptly and are affordable and accessible across the globe, particularly in the places where HIV transmission rates remain unacceptably high.”

See IAVI’s pipeline for a list of our HIV broadly neutralizing antibodies candidates.

For an overview of the trials and their implications, read “The AMP Trials — A Glass Half Full,” by Bruce D. Walker, M.D., in the NEJM.