Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251.
Effector cells armed with Abs can eliminate virus-infected target cells by Ab-dependent cellular cytotoxicity (ADCC), an immune mechanism that has been largely overlooked in HIV vaccine development. Here, we show that a prime/boost AIDS vaccine approach elicits potent ADCC activity correlating with protection against SIV in rhesus macaques (Macacca mulatta). Priming with replicating adenovirus type 5 host range mutant-SIV recombinants, followed by boosting with SIV gp120, elicited Abs with ADCC activity against SIV(mac251)-infected cells. In vitro ADCC activity correlated with in vivo reduced acute viremia after a mucosal challenge with pathogenic SIV. Our findings expose ADCC activity as an immune correlate that may be relevant in the rational design of an efficacious vaccine against HIV.
Gómez-Román
V Raúl
VR
Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Patterson
L Jean
LJ
Venzon
David
D
Liewehr
David
D
Aldrich
Kris
K
Florese
Ruth
R
Robert-Guroff
Marjorie
M
D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D015686:Gene Products, env / Q000276:immunology / Q000378:metabolism; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000502:physiology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D012189:Retrospective Studies; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019562:Viral Load; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*
D000914:Antibodies, Viral; D015686:Gene Products, env; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic