LAUSR

Background: Early steps of HIV infection are mediated by the binding of the envelope to mucosal receptors as &agr;4&bgr;7 and the C-type lectins DC-SIGN and langerin. Previously Env-specific B-cell responses have been reported in highly exposed seronegative individuals (HESN). Method: Here, we studied gp120-specific antibodies ability to block HIV interaction with &agr;4&bgr;7, DC-SIGN and/or langerinin HESN. New cell-based assays were developed to analyze whether antibodies that can alter gp120 binding to &agr;4&bgr;7, DC-SIGN and/or langerin are induced in HESN. A mucosal blocking score (MBS) was defined based on the ability of antibodies to interfere with gp120/&agr;4&bgr;7, gp120/DC-SIGN, and gp120/langerin binding. A new MBS was evaluated in a cohort of 86 HESN individuals and compared with HIV+ patients or HIV− unexposed healthy individuals. Results: Antibodies reducing gp120 binding to both &agr;4&bgr;7 and DC-SIGN were present in HESN serum but also in mucosal secretions, whereas antibodies from HIV+ patients facilitated gp120 binding to DC-SIGN. Any correlation was observed between MBS and the capacity of antibodies to neutralize infection of &agr;4&bgr;7+ CD4+ T cells with primary isolates. Conclusions: MBS is significantly associated with protection in HESN and might reflect altered HIV spreading to mucosal-associated lymphoid tissues.