HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1

Creators: Schoofs, Till; Klein, Florian; Braunschweig, Malte; Kreider, Edward F.; Feldmann, Anna; Nogueira, Lilian; Oliveira, Thiago Y.; Lorenzi, Julio C. C.; Parrish, Erica H.; Learn, Gerald H.; West, Anthony P., Jr.; Bjorkman, Pamela J.; Schlesinger, Sarah J.; Seaman, Michael S.; Czartoski, Julie; McElrath, M. Juliana; Pfeifer, Nico; Hahn, Beatrice H.; Caskey, Marina; Nussenzweig, Michel C.

Abstract

3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1–infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.

Additional Information

© 2016 American Association for the Advancement of Science. 17 December 2015; accepted 14 April 2016. Published online 5 May 2016. We thank all study participants, who devoted time to our research. We thank the Rockefeller University Hospital Clinical Research Support Office, the nursing staff for patient care and recruitment, the clinical study group of the Infectious Disease Division at the University Hospital Cologne, and all members of the Nussenzweig lab for helpful discussions. We thank M. Schechter and C. Baro for technical assistance, P. Fast and H. Park for clinical monitoring, E. Gotschlich and B. Coller for input on study design, and P. Hraber for helping with LASSIE analyses. The data reported in this study are tabulated in the main paper and in the supplementary materials. Envelope single-genome sequencing data can be downloaded from GenBank (accession numbers KX027737 to KX028736). This work was supported in part by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, grants OPP1032144 (M.S.S.) and OPP1092074 and OPP1124068 (M.C.N); the Robertson Foundation to M.C.N.; the NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, grants 1UM1 AI100663-01 (M.C.N) and 1UM1 AI00645 (B.H.H.); the University of Pennsylvania Center for AIDS Research Single Genome Amplification Service Center P30, grant AI045008 (B.H.H.); and NIH grants UM1AI068618 (M.J.M.), UM1AI069481 (M.J.M.), F30 AI112426 (E.F.K), and HIVRAD P01 AI100148 (P.J.B.). T.S. is supported by a Deutsche Forschungsgemeinschaft postdoctoral fellowship (grant SCHO 1612/1-1). F.K. is supported by the Heisenberg-Program of the Deutsche Forschungsgemeinschaft (grant KL 2389/2-1); the European Research Council (grant ERC-StG639961); and the German Center for Infection Research, partner site Bonn–Cologne, Cologne, Germany. M.B. is supported by the German National Academic Foundation. J.C.C.L. is supported by an award from the Conselho Nacional de Desenvolvimento Científico e Tecnológico "Ciencia sem Fronteiras" (grant 248676/2013-0). M.C.N. is a Howard Hughes Medical Investigator and an inventor on U.S Patent Application no. 14/118,496, filed by Rockefeller University related to 3BNC117.

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Accepted Version - nihms833243.pdf

Supplemental Material - 04/science.aaf0972.DC1/aaf0972-Schoofs-SM.pdf

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