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Three Neutralizing Antibody Lineages Identified from an HIV-1-Infected Individual

March 13, 2019

A new longitudinal analysis illuminates early events in the development of three neutralizing antibody lineages in an HIV-1-infected individual, insights which may help inform vaccine design. Researchers, led by scientists with the U.S. Military HIV Vaccine Research Program (MHRP) at the Walter Reed Army Institute of Research and the Vaccine Research Center at the National Institutes of Health, published their findings earlier this week in the journal Immunity.

Neutralizing antibodies against HIV-1 are likely to be a major component of the protective immune response elicited by an effective vaccine. Studying the structure, epitope recognition and development of broadly neutralizing antibodies (bNAbs) in infected individuals is likely to provide important clues for vaccine design. However, the lack of longitudinal and early samples in infection has limited the ability of such studies to uncover the earliest events in the development of these antibodies.

In the new study, researchers analyzed longitudinal samples from an HIV-1 infected individual who was part of MHRP’s RV217 acute infection cohort. RV217 is a multi-site study led by MHRP in East Africa that followed a group of high-risk volunteers, tracked their HIV status and characterized progression through the acute stages of HIV infection. This prospective study has captured samples from some of the earliest stages of HIV infection, along with blood samples before infection.

Antibodies in this individual targeted the membrane-proximal external region (MPER) of the HIV-1 envelope, a site of vulnerability that may hold promise as a potential HIV vaccine target. By following this individual over time, the researchers elucidated the early development of three MPER-targeting bNAb lineages, antibodies RV217-VRC42.01, VRC43.01 and VRC46.01, which arose between days 85-154 of infection. The three antibodies used distinct modes of virus recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. In addition, the researchers developed a potential immunogen that was able to initiate the lineage of the most broad antibody, VRC42.01, providing a potential pathway towards an effective vaccine strategy.

“By revealing some of the early events in the development of MPER-targeted antibodies, and identifying a candidate immunogen to elicit them, this work has yielded insights that may guide efforts in lineage-based vaccine design,” said co-author Dr. Shelly Krebs, chief of MHRP’s B cell biology core.