The battle against HIV-1, the virus that causes AIDS, has been ongoing for decades. Perhaps one of the most important advances in their understanding and fight against the virus has been the identification of a unique class of antibodies called broadly neutralising antibodies, or bNAbs. They have been found to have extraordinary potential for neutralising large panels of HIV strains and thus form the focus of vaccine research and future treatment strategies.
Turning point in 1994: Discovery of antibody b12
In 1994, a seminal study in the journal Science came out describing the isolation of one such antibody, termed b12. It was identified from an HIV-infected patient and had an unusually potent virus-neutralising ability. Previously, scientists had been investigating pooled plasma from HIV-infected patients. It had billions of diverse antibodies present. Even then, the pooled plasma could neutralise HIV from only 3 out of 12 patients.By way of comparison, the b12 alone performed as well in 8 of the 12 patients as the pooled plasma. This was a significant result, particularly as the antibody had been employed at a mere one-fifth concentration of the pooled plasma. The b12 antibody hit a region on the HIV virus’s envelope protein, gp120, that is famous for being one of the hardest components of the virus to target because it has a high mutation rate and a glycan shield. Binding to this vital location, b12 was able to prevent the virus from binding to and entering human immune cells.
A new gen of antibodies, a new hope
Since B12 was discovered, scientists everywhere have increased efforts to isolate more antibodies with the same characteristics. Several other bNAbs have been isolated from persons who had been living with HIV for extended years. Such persons, commonly known as “elite neutralisers,” developed strong antibodies themselves that could neutralize numerous various strains of HIV-1.Some of the most well-characterized bNAbs found since b12 are VRC01, PG9, PG16, 10-1074, and 3BNC117. They recognize distinct exposed sites on the HIV envelope, such as the CD4 binding site, the V1/V2 apex, and the V3 glycan patch. Their ability to neutralize broad panels of viral strains has made them top contenders for potential therapeutic use as well as for vaccine engineering.Experiments have shown that injection into non-human primates of a few of these antibodies provided protection against challenge with simian-human immunodeficiency virus (SHIV). Early clinical trials in humans also indicated that bNAbs could reduce viral load in HIV+ individuals and, when antiretroviral therapy was stopped, delay viral rebound.The identification and development of widely neutralising antibodies mark a significant step towards HIV control worldwide. Researchers are continuing to explore why these naturally occur in the body and to work on making vaccines that can stimulate similar reactions in healthy individuals.In the Indian context, researchers have discovered that broadly neutralizing antibodies (bNAbs) targeting the V3 glycan of Indian HIV strains were the most effective at neutralizing the virus, while antibodies directed at the V1/V2 apex of the viral spike protein showed much lower effectiveness in the pastEven as the scientific community continues to work toward finding an effective HIV vaccine and long-lasting treatments, the work of bNAbs like b12 is at the center of both understanding the disease and the dream of an HIV-free world tomorrow.