Fc receptor but not complement binding is important in antibody protection against HIV.
Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge. However, the mechanism(s) by which neutralizing antibodies afford protection against HIV is not understood and, in particular, the role of antibody Fc-mediated effector functions is unclear. Here we report that there is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody. No loss of antibody protective activity is associated with the elimination of complement binding alone. Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complexed infected cells is important in reducing virus yield from infected cells. Overall, the data suggest the potential importance of activity against both infected cells and free virus for effective protection against HIV.
Hessell
Ann J
AJ
Department of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Hangartner
Lars
L
Hunter
Meredith
M
Havenith
Carin E G
CE
Beurskens
Frank J
FJ
Bakker
Joost M
JM
Lanigan
Caroline M S
CM
Landucci
Gary
G
Forthal
Donald N
DN
Parren
Paul W H I
PW
Marx
Preston A
PA
Burton
Dennis R
DR
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D009500:Neutralization Tests; D011961:Receptors, Fc / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013997:Time Factors; D019562:Viral Load