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

Schoofs, Till and Klein, Florian and Braunschweig, Malte and Kreider, Edward F. and Feldmann, Anna and Nogueira, Lilian and Oliveira, Thiago and Lorenzi, Julio C. C. and Parrish, Erica H. and Learn, Gerald H. and West, Anthony P., Jr. and Bjorkman, Pamela J. and Schlesinger, Sarah J. and Seaman, Michael S. and Czartoski, Julie and McElrath, M. Juliana and Pfeifer, Nico and Hahn, Beatrice H. and Caskey, Marina and Nussenzweig, Michel C. (2016) HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science, 352 (6288). pp. 997-1001. ISSN 0036-8075. PMCID PMC5151174. http://resolver.caltech.edu/CaltechAUTHORS:20160601-145651018

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.aaf0972DOIArticle
http://science.sciencemag.org/content/352/6288/997PublisherArticle
http://www.sciencemag.org/content/352/6288/997/suppl/DC1PublisherSupplementary Materials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5151174/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Nussenzweig, Michel C.0000-0003-0592-8564
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.
Funders:
Funding AgencyGrant Number
Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine DiscoveryOPP1032144
Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine DiscoveryOPP1092074
Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine DiscoveryOPP1124068
Robertson FoundationUNSPECIFIED
NIH1UM1 AI100663-01
NIH1UM1 AI00645
NIHAI045008
NIHUM1AI068618
NIHUM1AI069481
NIHF30 AI112426
NIHP01 AI100148
Deutsche Forschungsgemeinschaft (DFG)SCHO 1612/1-1
Deutsche Forschungsgemeinschaft (DFG)KL 2389/2-1
European Research Council (ERC)ERC-StG639961
German Center for Infection ResearchUNSPECIFIED
Studienstiftung des deutschen VolkesUNSPECIFIED
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)248676/2013-0
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC5151174
Record Number:CaltechAUTHORS:20160601-145651018
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160601-145651018
Official Citation:HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1 BY TILL SCHOOFS, FLORIAN KLEIN, MALTE BRAUNSCHWEIG, EDWARD F. KREIDER, ANNA FELDMANN, LILIAN NOGUEIRA, THIAGO OLIVEIRA, JULIO C. C. LORENZI, ERICA H. PARRISH, GERALD H. LEARN, ANTHONY P. WEST JR., PAMELA J. BJORKMAN, SARAH J. SCHLESINGER, MICHAEL S. SEAMAN, JULIE CZARTOSKI, M. JULIANA MCELRATH, NICO PFEIFER, BEATRICE H. HAHN, MARINA CASKEY, MICHEL C. NUSSENZWEIG Science 20 May 2016: Vol. 352, Issue 6288, pp. 997-1001 DOI: 10.1126/science.aaf0972
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67555
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Jun 2016 15:44
Last Modified:26 Oct 2017 22:08

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