Antibodies are proteins that immune cells make to block viruses and other infectious agents. In the case of HIV, people who are infected typically produce antibodies to the virus. But because the virus mutates and replicates rapidly, antibodies are largely ineffective at controlling the virus. After years of infection, though, some people produce highly potent antibodies called broadly neutralizing antibodies (bnAbs) that, in laboratory tests, are able to neutralize a wide variety of HIV strains. The identification of such antibodies has transformed the field of HIV prevention research for two reasons: it provides information to guide the design of vaccines that could elicit bnAbs for protection, and it has opened the door to a new prevention modality: the administration of HIV bnAbs to prevent infection.
The administration of antibodies to prevent infection is known as passive immunization, in contrast to active immunization, which occurs as a result of vaccination (see graphic, below). 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. Several monoclonal antibodies against COVID-19 have been authorized by the FDA for emergency use during the pandemic.
But HIV-specific bnAbs could have a role in treating, preventing, or even curing HIV. And technological advances have enabled researchers to optimize antibodies to make them more potent and longer lasting, and to produce them outside the human body.
Some HIV-specific bnAbs are already being tested in clinical trials, both for prevention and treatment. Currently, IAVI is sponsoring two clinical trials of HIV bnAbs.
Access to antibodies
In complement with preclinical and clinical development of bnAbs, IAVI and partners are working to ensure that bnAbs, once shown to be efficacious, will be promptly, globally, and affordably accessible to the people who need them.
Our 2020 global call to action, commissioned by Wellcome, highlights the lack of equitable access to antibodies in low- and middle-income countries (LMICs). We proposed a set of actions that could solve the access problem:
- Build user preferences and local community needs into product development plans from the very beginning of the development process.
- Work with low-cost manufacturers and supporting innovations in production and delivery.
- Collaborate with regulatory bodies and policymakers across the world to ensure pathways exist for rapid registration, adoption, and distribution of bnAbs.
- Expand public-private partnerships to develop and commercialize affordable antibodies for global and sustainable access.