By IDSE News Staff
Neutralizing antibodies, including those described as broadly neutralizing, contribute to controlling HIV in post-treatment controllers (Cell Host Microbe 2023;31[8]:1275-1287.e8).
“Post-treatment controllers” refers to the rare HIV-1 carriers who, having initiated early antiretroviral therapy (ART) and maintained it for several years, are able to control the virus for years after ART has been discontinued. These individuals were identified several years ago in part through the VISCONTI study, which assembled the largest cohort of long-term, post-treatment controllers in France. Although the mechanisms of viral control enabling the long-term remission from HIV-1 infection without ART have not been fully elucidated, the identification of these cases provides a unique opportunity to refine our understanding of the factors associated with HIV-1 infection control, the researchers said.
They followed up on an earlier study on the immune response in post-treatment controllers with a deep dive into the immunity of one post-treatment controller case with particularly high serum levels of broadly neutralizing antibodies (bNAbs) and discovered that remission was probably linked to the activity of this type of antibodies, according to Asier Sáez-Cirión, PhD, the head of the Institut Pasteur’s Viral Reservoirs and Immune Control Unit, in Paris.
The antibody EPTC112 neutralizes about one-third of the 200 viral variants of HIV-1 tested in vitro and is able to induce the elimination of infected cells in the presence of natural killer cells, the immune cells eliminating abnormal cells in the body.
This study therefore provides insight about how neutralizing antibodies modify the course of HIV-1 infection in an individual from the VISCONTI cohort. Although the HIV-1 virus circulating in this person was found to be resistant to EPTC112 neutralization due to mutations in the region targeted by this antibody, it was effectively neutralized by other antibody populations isolated from the blood of the individual. Hence, the study suggests that neutralizing antibodies from the EPTC112 family impose selective pressure on the HIV-1 virus. Although the virus escaped the action of these bNAbs, it remained susceptible to the neutralization by other anti-HIV-1 antibodies produced in this individual. This observation suggests the existence of a cooperation between the various populations of neutralizing antibodies.
“The fact that we discovered a potential link between the production of neutralizing antibodies, including bNAbs, and the HIV-1 control is exciting to better understand the underlying mechanisms of viral control, particularly by studying additional post-treatment controllers with similar profiles. Indeed, we wish to continue investigating on a short term whether the antibody responses in other ‘post-treatment’ controllers also contribute to long-term remission from the infection,” explained Hugo Mouquet, PhD, the head of the Humoral Immunology Unit at the Institut Pasteur.
This discovery paves the way for new avenues of HIV-1 therapy and fuels hopes of therapeutic approaches for increasing the chances of remission without ART through the use of bNAbs.
To this end, a clinical trial involving the administration of bNAbs should begin in France before the end of the year.
“This phase 2 trial conducted by the ANRS RHIVIERA consortium through a partnership between the Institut Pasteur, AP-HP, Inserm and the Rockefeller University in New York, will investigate the combination of an antiretroviral therapy in the primary infection phase with two long-acting HIV-1 bNAbs versus placebo to determine whether these antibodies contribute to establishing viral remission after antiretroviral treatment discontinuation. Sixty-nine patients in the primary HIV-1 infection phase are planned to be enrolled. They will first receive a short-term antiretroviral treatment, followed by a therapy with the two bNAbs targeting two different regions of the virus envelope protein. It will be possible to stop therapy after a year of close monitoring based on a detailed set of criteria. This trial will enable us to determine whether this therapeutic strategy is able to induce a sufficient immune response to control the infection after the discontinuation of antiretroviral therapy," Dr. Mouquet said.
