CaltechAUTHORS
Published November 10, 2014 | Version Published
Journal Article Open

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

Creators

  • 1. ROR icon Rockefeller University
  • 2. ROR icon National Institute of Allergy and Infectious Diseases
  • 3. ROR icon Karolinska Institute
  • 4. ROR icon California Institute of Technology
  • 5. ROR icon University Hospital Cologne
  • 6. ROR icon New York University
  • 7. ROR icon Beth Israel Deaconess Medical Center
  • 8. ROR icon Harvard University
  • 9. ROR icon James J Peters VA Medical Center

Abstract

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.

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.

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Additional details

Identifiers

PMCID
PMC4235636
Eprint ID
51830
Resolver ID
CaltechAUTHORS:20141117-100446185

Funding

Stavros Niarchos Foundation
Robert Mapplethorpe Foundation
Swedish Research Council
International AIDS Vaccine Initiative
Karolinska Institutet
Bundesministerium für Bildung und Forschung (BMBF)
01KI1017
Deutsches Zentrum für Infektionsforschung (DZIF)
Bill and Melinda Gates Foundation
1032144
Bill and Melinda Gates Foundation
1040753
Bill and Melinda Gates Foundation
38619
National Center for Advancing Translational Sciences (NCATS)
UL1 TR00004
NIH
AI 100663-01
NIH
UM1AI100663
National Institute of Allergy and Infectious Diseases
NIH
AI 100148-01
NIH
P01 AI100151
NIH
R01 HL59725
Department of Veterans Affairs
Howard Hughes Medical Institute (HHMI)

Dates

Created
2014-11-17
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field