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J Exp Med. 2014 Nov 17;211(12):2361-72. doi: 10.1084/jem.20141050. Epub 2014 Nov 10.

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

Author information

1
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 fklein@rockefeller.edu.
2
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
3
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
4
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
5
Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125.
6
First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany.
7
Department of Pathology, NYU School of Medicine, New York, NY 10016.
8
Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125 Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125.
9
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
10
Department of Pathology, NYU School of Medicine, New York, NY 10016 Research Service, Veterans Affairs Medical Center, New York, NY 10010.
11
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.

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.

PMID:
25385756
PMCID:
PMC4235636
DOI:
10.1084/jem.20141050
[Indexed for MEDLINE]
Free PMC Article

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