Vaccines against viral diseases typically work because they elicit antibodies against the virus that prevent infection. Given the global variability of HIV, which results from the virus’s rapid replication and mutation rate, researchers widely agree that an optimal vaccine would stimulate the human immune system to make a specific type of antibodies, referred to as broadly neutralizing antibodies (bnAbs). These antibodies are effective against the majority of HIV isolates currently in circulation around the globe.
Current efforts to design vaccine candidates capable of inducing bnAbs are possible because of the identification of potent bnAbs from large-scale epidemiological studies of HIV-infected individuals. Learn more about the discovery of bnAbs. Thanks to these studies, some of which were pioneered by IAVI and its partners, researchers have now identified and characterized hundreds of HIV-specific bnAbs that occasionally develop over the course of natural HIV infection. These antibodies can neutralize a wide range of genetically variable HIV isolates in laboratory tests, and studies show that some bnAbs can protect monkeys against a virus similar to HIV. This suggests that a vaccine that could induce similar antibodies in people might protect them against HIV infection.
Using the latest tools in structural biology, scientists have also determined precisely how and where these broadly neutralizing antibodies interact with the virus. This information helps guide the development of a new generation of vaccine immunogens designed to stimulate the production of bnAbs through vaccination.
Passive administration of bnAbs
In addition to developing vaccine candidates that can induce bnAbs, IAVI and its partners are exploring strategies for directly delivering bnAbs to prevent HIV infection. This strategy is referred to as passive immunization, in contrast to active immunization, which occurs as a result of vaccination. While a vaccine “trains” the immune system to generate antibodies and other immune responses, passive immunization requires that the antibodies be delivered directly into the body through infusions or injections. This protection is temporary, and, in the case of HIV prevention, would need to be administered periodically as long as the subject was still at risk.
In contrast to the fields of oncology and rheumatology, in which advances in the therapeutic use of monoclonal antibodies (mAbs) have been revolutionary, only one infectious disease—anthrax—is currently treatable by a licensed mAb therapy (NEJM 378; 16; 2018). And only one antiviral monoclonal antibody is licensed in the U.S. It is administered for the prevention of respiratory syncytial virus in premature infants.
But the recently discovered HIV-specific bnAbs may have a role in treating, preventing, or even curing HIV. Technological advances have made it possible to identify, characterize, optimize, and manufacture antibodies like never before.
Some HIV-specific bnAbs are already being tested in clinical trials, both for prevention and treatment. IAVI scientists and their partners are working to optimize HIV-specific bnAbs, develop low-cost manufacturing processes to produce them, and eventually test their ability to prevent HIV infection. Antibody preventives, if effective, could augment existing HIV prevention strategies and help limit the spread of the virus until a vaccine is developed.
Opportunities for novel approaches to developing antibody products exist across the spectrum of infectious diseases, cancers, and chronic diseases. IAVI and partners are expanding their antibody discovery, optimization, and manufacturing expertise to develop antibody products for prevention and therapy of multiple diseases.
At the same time that discovery and development of these potential products are occurring, IAVI is working to ensure that future antibody treatments and preventives will be affordable and accessible to the people who need them. Current mAb treatments are expensive and therefore out of reach for most of the world’s population. New approaches to developing and advancing low-cost mAbs are urgently needed, and IAVI is working in innovative partnerships to solve this problem.
Learn more about IAVI’s work to develop monoclonal antibodies for snakebite treatment.