title: Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers.
abstract: Although HIV-specific cellular immune responses are found in a number of HIV highly-exposed, persistently seronegative (HEPS) cohorts, late seroconversion can occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesting that a protective HIV vaccine may need to induce a broader range of HIV-specific immune responses. Low levels of HIV-specific IgA have been found in the genital tract and plasma of the majority of Nairobi HEPS sex workers and appeared to be independent of HIV-specific cellular responses. IgA purified from genital tract, saliva and plasma of most HEPS sex workers were able to neutralize infection of PBMC by a primary (NSI) clade B HIV isolate, as well as viral isolates from clades A and D, which predominate in Kenya. In addition, these IgA were able to inhibit transcytosis of infective HIV virions across a transwell model of the human mucosal epithelium in an HIV-specific manner. Preliminary work in other HEPS cohorts has suggested the recognition of different gp41 epitopes in HEPS and HIV-infected subjects. Although present at low levels, these IgA demonstrated cross-clade neutralizing activity and were able to inhibit HIV mucosal transcytosis, suggesting an important functional role in protection against HIV infection.
authors.affiliation: Department of Clinical Virology, F68, Karolinska Institute, Huddinge University Hospital, S-141 86, Stockholm, Sweden. kristina.broliden@viruslab.hs.sll.se
authors.forename: K
authors.initials: K
authors.lastname: Broliden
authors.forename: J
authors.initials: J
authors.lastname: Hinkula
authors.forename: C
authors.initials: C
authors.lastname: Devito
authors.forename: P
authors.initials: P
authors.lastname: Kiama
authors.forename: J
authors.initials: J
authors.lastname: Kimani
authors.forename: D
authors.initials: D
authors.lastname: Trabbatoni
authors.forename: J J
authors.initials: JJ
authors.lastname: Bwayo
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.forename: F
authors.initials: F
authors.lastname: Plummer
authors.forename: R
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000918:Antibody Specificity; D015331:Cohort Studies; D000939:Epitopes; D005260:Female; D005836:Genitalia, Female / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000378:metabolism*; D015488:HIV Antigens; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood; D007630:Kenya; D009500:Neutralization Tests; D011477:Sex Work; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G