title: Mucosal exposure to subinfectious doses of SIV primes gut-associated antibody-secreting cells and T cells: lack of enhancement by nonneutralizing antibody.
abstract: It has been suggested that the presence of immunoglobulin and complement receptors on rectal epithelium may facilitate the entry of HIV complexed to nonneutralizing antibody. We tested this hypothesis using simian immunodeficiency 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 occurrence of rectal infection was compared with virus alone. Animals were not infected overtly and were rechallenged with a 10-fold higher dose of virus with and without addition of antibody. There was no evidence of antibody-mediated 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 responses generated. In seronegative animals, in which virus and proviral DNA were undetectable in PBMC and tissues, SIV-specific T-cell responses and antibody-secreting cells were found in systemic and gut-associated sites. Our results show that nonneutralizing antibody neither facilitated nor enhanced rectal infection with SIV, in the small number of animals used, despite the consistent trend for this antibody to enhance antibody responses to gp120 following rectal immunization with immune-complexed antigen. However, mucosal exposure to subinfectious doses of virus primed both systemic and local immunity, regardless of addition of nonneutralizing antibody.
authors.affiliation: Centre for Applied Microbiology and Research (CAMR), Salisbury, United Kingdom. natasha.polyanskaya@camr.org.uk
authors.forename: N
authors.initials: N
authors.lastname: Polyanskaya
authors.forename: L A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: S A
authors.initials: SA
authors.lastname: Sharpe
authors.forename: N
authors.initials: N
authors.lastname: Cook
authors.forename: S
authors.initials: S
authors.lastname: Leech
authors.forename: G
authors.initials: G
authors.lastname: Hall
authors.forename: M
authors.initials: M
authors.lastname: Dennis
authors.forename: P
authors.initials: P
authors.lastname: ten Haaft
authors.forename: J
authors.initials: J
authors.lastname: Heeney
authors.forename: F
authors.initials: F
authors.lastname: Manca
authors.forename: T
authors.initials: T
authors.lastname: Lehner
authors.forename: M P
authors.initials: MP
authors.lastname: Cranage
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D007110:Immunity, Active; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000032:analysis; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D012007:Rectum / Q000276:immunology* / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G