The Magic Bullet for HIV-1? Discovering the Powerhouse Antibody

A Potential Key to HIV-1 Management: Unveiling the Potent Antibody EPTC112

Antibody fragments of EPTC112 bNAb, identified by the research team led by Hugo Mouquet at Institut Pasteur, form a complex with the HIV-1 envelope protein, Env. The image is credited to Institut Pasteur and Hugo Mouquet.

Scientists have pinpointed “Post-treatment controllers” among HIV-1 carriers who are able to regulate the virus even after discontinuing medication. The antibody EPTC112 has been found to be instrumental in exerting this control, which brings to light new possibilities for treating HIV-1.

Individuals who have been administered early antiretroviral therapy for an extended period can continue to manage the virus well after the therapy has been halted. Nevertheless, the precise mechanisms behind this post-treatment control are not yet entirely understood. Researchers from Institut Pasteur, Inserm, and the Paris Public Hospital Network (AP-HP), in collaboration with ANRS | Emerging Infectious Diseases, have for the first time investigated the role of neutralizing antibodies, including broadly neutralizing antibodies, in virus control. These seminal findings were published in the scientific journal Cell Host & Microbe, and a clinical trial exploring the application of broadly neutralizing antibodies is slated to begin in France before the close of 2023.

Delving into the Phenomenon of “Post-treatment Controllers” and HIV-1

“Post-treatment controllers” is a term applied to a subset of HIV-1 carriers who have been treated early and have maintained treatment for a significant duration, only to exhibit long-term control over the virus once the treatment ceases. These individuals were primarily identified via the VISCONTI study, which amassed the most extensive group of long-term post-treatment controllers in France.

Although the exact mechanisms allowing for long-term viral suppression without the need for ongoing antiretroviral treatment are still unclear, the identification of such cases offers a unique lens through which to examine the variables related to controlling HIV-1 infection.

In-Depth Analyses on Immune Mechanisms

Research conducted by the Humoral Immunology Unit of Institut Pasteur, overseen by Dr. Hugo Mouquet and in collaboration with Dr. Asier Sáez-Cirión, is contributing to elucidate these mechanisms. Asier Sáez-Cirión states that a prior study published in 2020 was a significant first move in demonstrating a potent and resilient antibody response to HIV-1 in some post-treatment controllers, potentially contributing to the control.

The most recent research advances this understanding by examining the role of antibodies in a specific case of a “post-treatment controller” who had notably high levels of broadly neutralizing antibodies in their serum. It was found that remission was likely due to the action of these antibodies.

Functionality of EPTC112 Antibody

EPTC112 has been observed to neutralize nearly one-third of 200 tested viral variants of HIV-1 in vitro and is capable of initiating the removal of infected cells in collaboration with natural killer (NK) cells, which are immune cells tasked with eliminating aberrant cells. The findings offer considerable insight into how these antibodies alter the trajectory of HIV-1 infection in a subject from the VISCONTI cohort. Even though mutations made the virus in this individual resistant to EPTC112, it remained susceptible to neutralization by other antibodies present in the individual’s bloodstream, suggesting a synergy between various populations of neutralizing antibodies.

Opening Doors to Novel Treatment Approaches

Dr. Hugo Mouquet emphasizes that the link discovered between the generation of neutralizing antibodies and HIV-1 control is promising for understanding the mechanisms of viral management. A clinical trial is scheduled to commence in France before the end of 2023, with the aim of evaluating the efficacy of broadly neutralizing antibodies in treatment.

Forthcoming Clinical Trials

This Phase II trial will be administered by the ANRS RHIVIERA consortium, in a collaborative effort involving Institut Pasteur, AP-HP, Inserm, and the Rockefeller University in New York. The trial aims to explore the synergistic effects of antiretroviral therapy and two long-acting HIV-1 broadly neutralizing antibodies against a placebo. The study plans to enroll 69 patients in the primary phase of HIV-1 infection. These patients will first receive short-term antiretroviral therapy, followed by treatment with two broadly neutralizing antibodies. The study aims to determine the potential of this therapeutic strategy to elicit an adequate immune response to manage the infection post-discontinuation of antiretroviral treatment.

Notes

HIV: Investigating the Antibodies of “Post-treatment Controllers”
Article by Luis M. Molinos-Albert et al., published on 11 April 2022 in Nature Communications. DOI: 10.1038/s41467-022-29511-1
HIV-1 and HIV-2 are distinct at the molecular level, with different degrees of transmissibility, virulence, and immunogenicity, owing to their respective mutations.
For more details, visit https://rhiviera.com/project/anrs-rhiviera-02/
Primary infection is the initial stage of HIV-1 infection characterized by a high viral load and the invasion of the body’s immune system, specifically the CD4 lymphocyte reservoirs.
Reference: Article by Luis M. Molinos-Albert et al., published on 10 July 2023 in Cell Host & Microbe. DOI: 10.1016/j.chom.2023.06.006

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Frequently Asked Questions (FAQs) about HIV-1 Antibody EPTC112

More about HIV-1 Antibody EPTC112

• Nature Communications Article on HIV-1 Antibodies: The full article discussing the antibodies of “Post-treatment controllers” in HIV-1 carriers.

• Cell Host & Microbe Article on EPTC112 Antibody: The comprehensive study detailing the role of the EPTC112 antibody and its potential implications for HIV-1 treatment.

• ANRS RHIVIERA Project: Information about the ANRS RHIVIERA consortium’s project involving broadly neutralizing antibodies in HIV-1 therapy.

• Institut Pasteur: The official website of Institut Pasteur, a prominent research institute involved in this research.

• Inserm: The official website of Inserm, the French National Institute of Health and Medical Research, which played a role in this study.

• Paris Public Hospital Network (AP-HP): The official website of AP-HP, which collaborated in the research on HIV-1 management.

• Rockefeller University: The official website of the Rockefeller University, a partner in the clinical trial involving broadly neutralizing antibodies for HIV-1.

• VISCONTI Study: Information about the VISCONTI study, which identified “Post-treatment controllers” in HIV-1 carriers.