4.7 Article

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

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 211, Issue 12, Pages 2361-2372

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20141050

Keywords

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Funding

  1. Stavros Niarchos Foundation
  2. Robert Mapplethorpe Foundation
  3. Swedish Research Council
  4. International AIDS Vaccine Initiative
  5. Karolinska Institutet
  6. Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) [01KI1017]
  7. German Centre for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany
  8. Bill and Melinda Gates Foundation
  9. Comprehensive Antibody Vaccine Immune Monitoring Consortium Grant [1032144]
  10. Collaboration for AIDS Vaccine Discovery Grants [1040753, 38619]
  11. National Center for Advancing Translational Sciences (NCATS) [UL1 TR000043]
  12. CHAVI-ID [UM1AI100663]
  13. National Institute of Allergy and Infectious Diseases, National Institutes of Health
  14. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [AI 100148-01]
  15. National Institutes of Health [P01 AI100151, R01 HL59725]
  16. Department of Veterans Affairs
  17. [AI 100663-01]

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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.

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