Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants.
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.
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 fklein@rockefeller.edu.
Florian
F
Klein
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Lilian
L
Nogueira
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Yoshiaki
Y
Nishimura
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Ganesh
G
Phad
Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125.
Anthony P
AP
West
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Ariel
A
Halper-Stromberg
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Joshua A
JA
Horwitz
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Anna
A
Gazumyan
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Cassie
C
Liu
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Thomas R
TR
Eisenreich
First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany.
Clara
C
Lehmann
First Department of Internal Medicine, University Hospital of Cologne, D-50924 Cologne, Germany.
Gerd
G
Fätkenheuer
Department of Pathology, NYU School of Medicine, New York, NY 10016.
Constance
C
Williams
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Masashi
M
Shingai
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Malcolm A
MA
Martin
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.
Pamela J
PJ
Bjorkman
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215.
Michael S
MS
Seaman
Department of Pathology, NYU School of Medicine, New York, NY 10016 Research Service, Veterans Affairs Medical Center, New York, NY 10010.
Susan
S
Zolla-Pazner
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Gunilla B
GB
Karlsson Hedestam
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.
Michel C
MC
Nussenzweig
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008253:Macaca mulatta; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009154:Mutation / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load / Q000276:immunology
D057134:Antibodies, Neutralizing; D014759:Viral Envelope Proteins