Human immunodeficiency virus 1 (HIV-1) is the virus responsible for most cases of acquired immunodeficiency syndrome (AIDS). It remains a major and worldwide public health issue, with millions of new cases reported every year. The development of a preventive vaccine has proven difficult due to the virus's variability and its immune-evasive mechanisms.

HIV-1 is found in diverse bodily fluids (e.g., blood, semen, vaginal secretions) as either free-floating ("cell-free") virions or within infected cells ("cell-associated" virus).

Although both manifestations play a role in viral spread, cell-associated transmission has often been underestimated in prevention measures. Earlier works performed in non-human primate models have shown that cell-associated transmission is dominant in the vaginal and colorectal routes. Studies have also suggested that infection in humans is initiated by these infected cells. These aspects emphasize the importance of targeting cell-associated transmission to effectively counter HIV-1 propagation.

The administration of broadly neutralizing HIV-1 antibodies (bNAbs), a passive immunity approach, has shown great therapeutic or preventive interest over the last few years, lifting these molecules to the rank of potentially ideal candidates for an HIV-1 vaccine. BNAbs target conserved viral epitopes, making them effective against a wide range of HIV-1 strains. Moreover, the protective action of these antibodies involves the activation of various immune system mechanisms.

But, to date, little work has been done to test the efficacy of bNAbs in the setting of cell-associated transmission.

To address this absence, researchers from IDMIT, with colleagues from Institut Pasteur and Chimie ParisTech, decided to study passive immunization using a specific bNAb, catchingly named "10-1074," in a preclinical model of infection employing the simian-human immunodeficiency virus. This latter, abbreviated "SHIV," is a chimeric virus used in scientific studies. It comprises both human and simian immunodeficiency virus genes.

In their study published in Nature Communications, the researchers showed that the vaginal mucosal application of 10-1074 provided significant protection against repeated vaginal exposure to cell-associated SHIV. Beyond demonstrating 10-1074's efficacy in preventing cell-associated viral transmission, the team also established the antibody concentration needed to ensure optimal protection. Their results also underline the importance of the employed antibody's formulation and route of administration: a microbicidal gel for topical vaginal application, which lays the groundwork for an employable means of preventing the sexual transmission of HIV. Going forward, it will be interesting to look at other neutralizing antibodies, in isolation or in combination, with the goal of reproducing these results and ensuring larger-spectrum protection.

With their demonstration of the efficacy of broadly neutralizing antibodies in cell-associated transmission in a preclinical model, the IDMIT researchers and their colleagues have laid a path toward the conception of more robust clinical trials. Their results bring new hope for significant advances in the battle against HIV-1 and the protection of people exposed to the virus.