Mucosal exposure to subinfectious doses of SIV primes gut-associated antibody-secreting cells and T cells: Lack of enhancement by nonneutralizing antibody

It has been suggested that the presence of immunoglobulin and complement re ceptors on rectal epithelium may facilitate the entry of HIV complexed to n onneutralizing antibody. We tested this hypothesis using simian immunodefic iency virus (SIV) infection of rhesus macaques. First, in a pilot study, a nonneutralizing IgG fraction of macaque anti-SIV gp120 was shown to enhance the immunogenicity of SIV envelope following rectal immunization. The same antibody was then mixed with a subinfectious dose of SIV and the occurrenc e of rectal infection was compared with virus alone. Animals were not infec ted overtly and were rechallenged with a 10-fold higher dose of virus with and without addition of antibody. There was no evidence of antibody-mediate d infection, since equal numbers of macaques became infected, regardless of the presence of antibody. In addition, the application of immune complexes did not alter significantly the subsequent virus load or the immune respon ses generated. In seronegative animals, in which virus and proviral DNA wer e undetectable in PBMC and tissues, SIV-specific T-cell responses and antib ody-secreting cells were found in systemic and gut-associated sites. Our re sults show that nonneutralizing antibody neither facilitated nor enhanced r ectal infection with SIV, in the small number of animals used, despite the consistent trend for this antibody to enhance antibody responses to gp120 f ollowing rectal immunization with immune-complexed antigen. However, mucosa l exposure to subinfectious doses of virus primed both systemic and local i mmunity, regardless of addition of nonneutralizing antibody, (C) 2001 Acade mic Press.