Cloning and characterization of novel IgA antibody variable heavy and light chains from HIV-1 resistant sex workers from Nairobi, Kenya

Abstract

Heterosexual intercourse now accounts for the majority of HIV transmission within sub-Saharan Africa. The generation of microbicides and vaccines, therefore, requires a better understanding of the mucosal correlates of protection, including the role of HIV-specific IgA.

It is now accepted that not all individuals are equally susceptible to HIV-1 infection, as exemplified by the HIV Exposed Seronegative (HESN) women of the Pumwani Cohort in Nairobi, Kenya. To assess whether mucosal IgA responses contribute to this protection, 3 novel IgA variable genes were cloned from HESN cervical B-cell cDNA.

Nine monoclonal IgA Abs were produced, two of which were properly produced from cell culture. The HESN-derived A6/30L and A9/30L variants had a greater specificity for gp120IIIB than their A6/4L and A9/4L counterparts, while the A6 variant recognizes a distinct gp120 epitope compared to the broadly neutralizing antibody IgGb12. Further characterization of these IgA chains may suggest their suitability for use in microbicides or mucosal vaccines.