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 administration or immunoprophylaxis. 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 repeat infusions or injections.

In contrast to the field of oncology, which has been revolutionized by advances in the therapeutic use of monoclonal antibodies, only a handful of antibody therapies are currently licensed for infectious diseases (NEJM 378; 16; 2018). And only one antiviral monoclonal antibody is currently in widespread use. 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 immunoprophylaxis, if effective, could augment existing HIV prevention strategies and help limit the spread of the virus until a vaccine is developed.

 

bnAbs journal.pmed.1002436.g001An illustration of the principles of using a monoclonal antibody as passive immunization to prevent HIV infection, as compared with the more traditional vaccine approach of active immunization. Created by Nolo Moima, Sunday Times, and Carina Kriel, NICD. Used with permission from PLOS Medicine.