Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies.
Although antibodies to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been studied extensively for their ability to block viral infectivity, little data are currently available on nonneutralizing functions of these antibodies, such as their ability to eliminate virus-infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 Env-specific antibodies of diverse specificities, including potent broadly neutralizing and nonneutralizing antibodies, were therefore tested for ADCC against cells infected with a lab-adapted HIV-1 isolate (HIV-1NL4-3), a primary HIV-1 isolate (HIV-1JR-FL), and a simian-human immunodeficiency virus (SHIV) adapted for pathogenic infection of rhesus macaques (SHIVAD8-EO). In accordance with the sensitivity of these viruses to neutralization, HIV-1NL4-3-infected cells were considerably more sensitive to ADCC, both in terms of the number of antibodies and magnitude of responses, than cells infected with HIV-1JR-FL or SHIVAD8-EO ADCC activity generally correlated with antibody binding to Env on the surfaces of virus-infected cells and with viral neutralization; however, neutralization was not always predictive of ADCC, as instances of ADCC in the absence of detectable neutralization, and vice versa, were observed. These results reveal incomplete overlap in the specificities of antibodies that mediate these antiviral activities and provide insights into the relationship between ADCC and neutralization important for the development of antibody-based vaccines and therapies for combating HIV-1 infection.



This study provides fundamental insights into the relationship between antibody-dependent cell-mediated cytotoxicity (ADCC) and virus neutralization that may help to guide the development of antibody-based vaccines and immunotherapies for the prevention and treatment of HIV-1 infection.
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Benjamin
B
von Bredow
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Juan F
JF
Arias
New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
Lisa N
LN
Heyer
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Brian
B
Moldt
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Khoa
K
Le
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA.
James E
JE
Robinson
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Susan
http://orcid.org/0000-0002-0750-2666
S
Zolla-Pazner
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.|International AIDS Vaccine Initiative Neutralizing Antibody Center, The Collaboration for AIDS Vaccine Discovery (CAVD), and Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, California, USA.|Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA.
Dennis R
DR
Burton
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA dtevans2@wisc.edu.|Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, USA.
David T
DT
Evans
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D001666:Binding Sites, Antibody; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000378:metabolism
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus