Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants-Reference-Cited by-同舟云学术

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

Published:2014-11-10 Issue:12 Volume:211 Page:2361-2372
ISSN:1540-9538
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Klein Florian¹,Nogueira Lilian¹,Nishimura Yoshiaki²,Phad Ganesh³,West Anthony P.⁴,Halper-Stromberg Ariel¹,Horwitz Joshua A.¹,Gazumyan Anna¹,Liu Cassie¹,Eisenreich Thomas R.¹,Lehmann Clara⁵,Fätkenheuer Gerd⁵,Williams Constance⁶,Shingai Masashi²,Martin Malcolm A.²,Bjorkman Pamela J.⁴⁴,Seaman Michael S.⁷,Zolla-Pazner Susan⁶⁸,Karlsson Hedestam Gunilla B.³,Nussenzweig Michel C.¹¹

Affiliation:

1. Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065

2. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

3. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

4. Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125

5. First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany

6. Department of Pathology, NYU School of Medicine, New York, NY 10016

7. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

8. Research Service, Veterans Affairs Medical Center, New York, NY 10010

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

http://rupress.org/jem/article-pdf/211/12/2361/1211949/jem_20141050.pdf

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