Neutralizing Antibodies Against a Specific Human Immunodeficiency Virus gp41 Epitope are Associated With Long-term Non-progressor Status

Abstract

Antibodies (Abs) play a central role in human immunodeficiency virus (HIV) protection due to their multiple functional inhibitory activities. W614A-3S Abs recognize a specific form of a highly conserved motif of the gp41 envelope protein and can elicit viral neutralization to protect CD4 ⁺ T cells. Here, we describe in detail the neutralizing profile of W614A-3S Abs in untreated long-term non-progressor (LTNP) HIV-infected patients. W614A-3S Abs were detected in 23.5% (16/68) of untreated LTNP patients compared with < 5% (5/104) of HIV-1 progressor patients. The W614A-3S Abs had efficient neutralizing activity that inhibited transmitted founder primary viruses and exhibited Fc-mediated inhibitory functions at low concentrations in primary monocyte-derived macrophages. The neutralizing capacity of W614A-3S Abs was inversely correlated with viral load ( r = − 0.9013; p < 0.0001), viral DNA ( r = − 0.7696; p = 0.0005) and was associated the preservation of high CD4 ⁺ T-cell counts and T-cell responses. This study demonstrates that W614A-3S neutralizing Abs may confer a crucial advantage to LTNP patients. These results provide insights for both pathophysiological research and the development of vaccine strategies.

Highlights

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  Long-term non-progressor patients produce W614A-3S neutralizing antibodies (NAb).

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  Neutralizing capacity of W614A-3S was correlated with viral load, CD4 count, and T-cell responses.

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  W614A-3S NAbs can be used in functional “cure” and vaccine strategies.

Long-term non-progressors (LTNPs) are individuals infected with HIV, who maintain a high CD4 count without antiretroviral therapy. Understanding the mechanisms implicated in this process will help in developing efficient HIV vaccine. We show that in contrast to treated HIV-1-infected patients, LTNPs individuals produce specific antibodies able to control the virus while preserving CD4 count and T-cell responses. This could form the basis for the development of future treatments or vaccine strategies based on W614A-3S to fight HIV-1.