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Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

Klein, Florian and Nogueira, Lilian and Nishimura, Yoshiaki and Phad, Ganesh and West, Anthony P., Jr. and Halper-Stromberg, Ariel and Horwitz, Joshua A. and Gazumyan, Anna and Liu, Cassie and Eisenreich, Thomas R. and Lehmann, Clara and Fätkenheuer, Gerd and Williams, Constance and Shingai, Masashi and Martin, Malcolm A. and Bjorkman, Pamela J. and Seaman, Michael S. and Zolla-Pazner, Susan and Karlsson Hedestam, Gunilla B. and Nussenzweig, Michel C. (2014) Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. Journal of Experimental Medicine, 211 (12). pp. 2361-2372. ISSN 0022-1007. PMCID PMC4235636. doi:10.1084/jem.20141050.

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Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian–human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Bjorkman, Pamela J.0000-0002-2277-3990
Nussenzweig, Michel C.0000-0003-0592-8564
Additional Information:© 2014 Klein et al. After six months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license. Submitted: 3 June 2014; accepted: 14 October 2014. We thank all HIV-1–infected individuals who participated in this study; Gisela Kremer for patient coordination; Reha-Baris Incesu for IgG purification; Israel Tojal Silva for sequence alignments; and Johannes Scheid and Hugo Mouquet for providing antibody plasmids. F. Klein was supported by the Stavros Niarchos Foundation and the Robert Mapplethorpe Foundation. G.B. Karlsson Hedestam and G. Phad were supported by grants from the Swedish Research Council, the International AIDS Vaccine Initiative and Karolinska Institutet. C. Lehmann was supported by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) grant 01KI1017. C. Lehmann and G. Fätkenheuer were supported by the the German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany. This work was supported in part by the Bill and Melinda Gates Foundation with Comprehensive Antibody Vaccine Immune Monitoring Consortium Grant 1032144 (to M.S. Seaman) and Collaboration for AIDS Vaccine Discovery Grants 1040753 (to P.J. Bjorkman) and 38619 (to M.C. Nussenzweig). This work was also supported in part by grant #UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), AI 100663-01 and CHAVI-ID Award UM1AI100663 (to M.C. Nussenzweig), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to M.A. Martin), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, AI 100148-01 (to P.J. Bjorkman and M.C. Nussenzweig), and National Institutes of Health grant P01 AI100151 and R01 HL59725 (to S. Zolla-Pazner), and research funds from the Department of Veterans Affairs (to S. Zolla-Pazner). P.J. Bjorkman and M.C. Nussenzweig are Howard Hughes Medical Institute Investigators. The authors declare no competing financial interests.
Funding AgencyGrant Number
Stavros Niarchos FoundationUNSPECIFIED
Robert Mapplethorpe FoundationUNSPECIFIED
Swedish Research CouncilUNSPECIFIED
International AIDS Vaccine InitiativeUNSPECIFIED
Karolinska InstitutetUNSPECIFIED
Bundesministerium für Bildung und Forschung (BMBF)01KI1017
Deutsches Zentrum für Infektionsforschung (DZIF)UNSPECIFIED
Bill and Melinda Gates Foundation1032144
Bill and Melinda Gates Foundation1040753
Bill and Melinda Gates Foundation38619
National Center for Advancing Translational Sciences (NCATS)UL1 TR00004
NIHAI 100663-01
National Institute of Allergy and Infectious DiseasesUNSPECIFIED
NIHAI 100148-01
NIHP01 AI100151
NIHR01 HL59725
Department of Veterans AffairsUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC4235636
Record Number:CaltechAUTHORS:20141117-100446185
Persistent URL:
Official Citation:Klein, F., Nogueira, L., Nishimura, Y., Phad, G., West, A. P., Halper-Stromberg, A., . . . Nussenzweig, M. C. (2014). Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. The Journal of Experimental Medicine, 211(12), 2361-2372. doi: 10.1084/jem.20141050
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51830
Deposited By: Jason Perez
Deposited On:17 Nov 2014 20:51
Last Modified:10 Nov 2021 19:16

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