Anti-cellular Antibodies in Sera from Vaccinated Macaques Can Induce Complement-Mediated Virolysis of Human Immunodeficiency Virus and Simian Immunodeficiency Virus

Abstract

Previous studies show that immunization of macaques with preparations of either human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) that has been produced in human ceils can induce antibodies against both viral antigens and human cellular antigens. This is due to the fact that certain host cell antigens are carried along with the virus during the purification process. The current series of experiments were performed to determine whether these anti-cellular antibodies can activate complement and whether the resultant complement activation could lead to virolysis of either HIV or SIV. Sera from macaques immunized with SIV or HIV (produced in the H9 human cell line) contained anti-cellular antibodies as determined by flow cytometry. Antibodies in these sera were capable of activating complement on uninfected human cells. Sera from the HIV-immunized macaques induced complement-mediated virolysis of both HIV and SIV. Similarly, sera from SIV-immunized macaques induced complement-mediated virolysis of both SIV and HIV. These results suggested that anti-cellular antibody in the sera could induce complement-mediated virolysis of either virus. To investigate this further, sera was absorbed with uninfected cells, which removed all of the virolytic activity for the heterologous virus. These in vitro studies indicate that complement activation can be initiated by anti-human cell antibodies, and that this activation can result in the destruction either HIV or SIV. This unusual antiviral mechanism may account for some portion of the resistance of human cell-immunized macaques to human cell-produced SIV that has been recently reported.