Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells

HIV-1-specific IgA has been described in the genital tract and plasma of HI V-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA f rom these sites has been shown to neutralize HIV-1, This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis acro ss a tight epithelial cell layer, A Transwell system was established to mod el HIV-1 infection across the human mucosal epithelium, The apical-basolate ral transcytosis of primary HIV-1 isolates across this mucosal model was ex amined in the presence and the absence of IgA isolated from the genital tra ct, saliva, and plasma of HEPS individuals enrolled in both a sex worker co hort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the abs ence of IgA, HIV-1 primary isolates were actively transported across the ep ithelial membrane and were released on the opposite side of the barrier. Th ese transcytosed HIV-1 particles retained their ability to infect human mon onuclear cells, However, IgA purified from the mucosa and plasma of HEPS in dividuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in th ree of six cervicovaginal fluid samples, five of 10 saliva samples, and thr ee of six plasma samples against at least one of the two primary HIV-1 isol ates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhi bit HIV-1 transcytosis across the mucosal epithelium may represent an impor tant mechanism for protection against the sexual acquisition of HIV-1 infec tion in REPS individuals.