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

Although HIV-specific cellular immune responses are found in a number of HI V highly-exposed, persistently seronegative (HEPS) cohorts, late seroconver sion can occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesti ng 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 i n the genital tract and plasma of the majority of Nairobi HEPS sex workers and appeared to be independent of HIV-specific cellular responses. IgA puri fied from genital tract, saliva and plasma of most HEPS sex workers were ab le 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 v irions across a transwell model of the human mucosal epithelium in an HIV-s pecific manner. Preliminary work in other HEPS cohorts has suggested the re cognition of different gp41 epitopes in HEPS and HIV-infected subjects. Alt hough present at low levels, these IgA demonstrated cross-clade neutralizin g activity and were able to inhibit HIV mucosal transcytosis, suggesting an important functional role in protection against HIV infection. (C) 2001 El sevier Science B.V. All rights reserved.