Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers

• Published in: Immunology letters Vol. 79; no. 1; pp. 29 - 36
• Main Authors: Broliden, Kristina, Hinkula, Jorma, Devito, Claudia, Kiama, Peter, Kimani, Joshua, Trabbatoni, Daria, Bwayo, Job J, Clerici, Mario, Plummer, Francis, Kaul, Rupert
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2001
• Subjects: Antibody Specificity; Cohort Studies; Epitopes; Female; Genitalia, Female - immunology; HIV Antibodies - blood; HIV Antibodies - metabolism; HIV Antigens; HIV Infections - immunology; HIV Infections - prevention & control; HIV resistance; HIV Seronegativity - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Humoral immunity; Immunity, Innate; Immunity, Mucosal; Immunoglobulin A - blood; Immunoglobulin A - metabolism; Immunoglobulin G - blood; Kenya; Neutralization; Neutralization Tests; Sex Work; T-Lymphocytes, Helper-Inducer - immunology; Transcytosis; Kenya; Transcytosis; HIV resistance; Humoral immunity; Neutralization
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/S0165-2478(01)00263-2

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.