HIV region-wise variations may affect antibody protection, may not work for differing strains: What are takeaways from new study

In the absence of a vaccine, injectable antibodies are currently being tested as a way to prevent HIV infection. A vaccine usually triggers the body’s own immune mechanism to produce antibodies against a specific disease. Antibodies are proteins made by the immune system that are able to recognise and neutralise foreign disease-causing organisms like viruses or bacteria. Since a vaccine against HIV is still not available, scientists have been testing the efficacy of injecting specific antibodies, identified and isolated in the laboratories, that have been found to prevent infection by HIV.

Different variants of HIV in circulation

There are several variants, or clades, of HIV in circulation. The most widely-circulating variant, called HIV-1 Clade C, accounts for nearly half of all infections across the world. This is also the most common variant circulating in Africa and India.

HIV mutates very quickly after infecting a person, sometimes creating millions of slightly different versions of itself. Most antibodies are unable to fight against, or neutralise, all of them. However, scientists have been able to identify and isolate some rare antibodies that can neutralise a large number of these slightly different variants. For this reason, these antibodies are called broadly-neutralising antibodies, or bnAbs.

Because these were found to be ‘broadly neutralising’, scientists were working on the assumption that they would be equally effective everywhere and against every variant of HIV.

Customising antibodies for India

However, the new Indian study has shown that the effectiveness of these bnAbs was affected by the geographical origin of the virus. This multi-centre study, which was supported by DBT/Wellcome Trust India Alliance funded Team Science Grant, has provided the first thorough evidence that HIV-1 clade C strains circulating in India differ from those primarily found in Africa in terms of their genomic composition and neutralization susceptibility to clinically-relevant bnAbs.

“This study has provided vital insights into the potential of broadly neutralizing antibodies (bnAbs) to transform HIV prevention and treatment,” Dr Jayanta Bhattacharya, Dean, BRIC-Translational Health Science and Technology Institute (THSTI) at Faridabad and corresponding author of the study told The Indian Express.

BRIC-THSTI, an autonomous institute under the Department of Biotechnology, Ministry of Science and Technology, through various partnerships, has been driving the development of therapeutic monoclonal antibodies as vital public health products. The institute is also working with a large network of collaborators from different institutions in India, Africa and International AIDS Vaccine Initiative (IAVI).

This study provides compelling evidence for the urgent need to follow up with the development of suitable monoclonal antibody products and initiate early-phase clinical trials in India, the authors of the study said.

Bhattacharya said, despite no preventive HIV vaccine, promising progress had been made that suggest that significant reduction in infection rates among high-risk groups and key populations can be achieved through the use of broadly neutralizing monoclonal antibodies administered along with antiretroviral therapy. He said that antiretroviral therapy (ART), in which patients are administered drugs that stop the replication of the virus in their bodies, had been successful in the treatment of HIV and slowed down the spread of the initial pandemic.

“However, rising global resistance to available antiretrovirals necessitates the expansion of available therapeutics and has reinvigorated efforts to design effective vaccines,” he said.

For this study, the researchers carried out virological and immunological surveillance of HIV across nine regions in the country. Their findings showed how the monitoring of circulating HIV helps assess how well leading (bnAbs) work against HIV-1 subtype C strains found in India and South Africa, which together account for most of the global HIV burden. “Data from this study provides critical insights for developing region-specific HIV prevention strategies, either by designing vaccines that can trigger strong antibody responses or by using passive immunization for individuals at high risk,” Bhattacharya said.

Mapping drug resistance

This study also identified pre-treatment drug resistance in up to 11 per cent of participants and according to the authors this finding highlighted a growing concern in HIV management.

“During our study we were able to screen (by deep sequencing) about 140 drug-naive HIV positive individuals that showed about 11 per cent pre-treatment antiretroviral drug resistance,” he said, adding that their research strongly suggested that bnAb combinations, when used with current antiretroviral therapy (ART), can effectively combat these drug-resistant HIV strains and improve prevention and treatment outcomes.

“This aligns with proofs-of-concept from trials like the Phase 2B Antibody Mediated Prevention Trial which showcased bnAb combinations as a powerful alternative for HIV prevention, particularly in vulnerable populations,” Dr Bhattacharya added.

He also observed that this study highlights that monoclonal antibodies are a high-value area for development and investment. “There is a need and sizeable market for innovative therapeutic agents that can address drug-resistant HIV,” Dr Bhattacharya said. Study authors have called for prioritization of locally relevant bnAbs.

“Identifying and selecting bnAbs appropriate for comprehensive neutralization of circulating Indian strains will be crucial,” study authors said.