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Enhanced clearance of HIV-1–infected cells by broadly neutralizing antibodies against HIV-1 in vivo

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Science  20 May 2016:
Vol. 352, Issue 6288, pp. 1001-1004
DOI: 10.1126/science.aaf1279

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Insights into antibody therapy for HIV-1

Despite the success of antiretroviral therapy, HIV-1-infected individuals still harbor latent virus. Thus, other therapeutic strategies are needed. A single injection of a broad and potent monoclonal antibody targeting the HIV-1 envelope protein reduced viral loads in HIV-1-infected individuals, albeit only transiently. Lu et al. now report that antibody treatment not only blocked free virus from infecting new cells, it also accelerated the clearance of infected cells. Furthermore, Schoofs et al. demonstrate that therapeutic antibody treatment enhanced infected individuals' humoral response against the virus. Thus, neutralizing antibodies may be a promising therapy for HIV-1 because of their potential to reduce the viral reservoir.

Science, this issue pp. 1001 and 997

Abstract

Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1–infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4+ T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1–infected cells.

  • * D.K.M. led the computational studies.

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