Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic

Abstract

Combination anti-retroviral therapy (ART) has revolutionized the treatment and prevention of HIV-1 infection. Taken daily, ART prevents and suppresses the infection. However, ART interruption almost invariably leads to rebound viremia in infected individuals due to a long-lived latent reservoir of integrated proviruses. Therefore, ART must be administered on a life-long basis. Here we review recent preclinical and clinical studies suggesting that immunotherapy may be an alternative or an adjuvant to ART because, in addition to preventing new infections, anti-HIV-1 antibodies clear the virus, directly kill infected cells and produce immune complexes that can enhance host immunity to the virus.

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Fig. 1: Approved monoclonal antibodies and bNAbs tested in clinical trials.
Fig. 2: bNAb characteristics and virus and host factors determine efficacy of passive immunotherapy for HIV-1 prevention and therapy.

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Acknowledgements

We thank members of the Klein and Nussenzweig laboratories for discussion. This work was supported by the NIH/National Institute of Allergy and Infectious Diseases Grant (U01AI129825), the Einstein-Rockefeller-CUNY Center for AIDS Research (1P30AI124414-01A1) and the BEAT-HIV Delaney grant UM1 AI126620 (M.C.); the Heisenberg-Program of the DFG (KL 2389/2-1), the European Research Council (ERC-StG639961) and the German Center for Infection Research (DZIF) (F.K.); the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1092074 and OPP1124068 and the NIH grants 1UM1 AI100663 and R01AI-129795 (M.C.N.); and the Robertson fund.

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Correspondence to Marina Caskey or Florian Klein or Michel C. Nussenzweig.

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There are patents on 3BNC117 and 10-1074, on which M.C.N is an inventor.

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Caskey, M., Klein, F. & Nussenzweig, M.C. Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic. Nat Med 25, 547–553 (2019). https://doi.org/10.1038/s41591-019-0412-8

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