Replicating Ad-HIV or Ad-SIV mucosal priming and envelope protein boosting elicits potent immunity and strong protection against viral challenges in non-human primates. Vaccine-elicited antibody activities correlated with protection include antibody-dependent cellular cytotoxicity and antibody-dependent cell-mediated viral inhibition. Both are correlated with reduced viremia and antibody avidity. IgG and IgA memory B cells in blood and bone marrow of vaccinated macaques, also correlated with reduced viremia, recall these activities. Further, IgG and IgA in rectal secretions of vaccinated macaques mediate transcytosis inhibition of virus across epithelial cells, an activity correlated with reduced viremia post-challenge. Recently, we investigated 4 mucosal routes of Ad-SIV recombinant priming (sublingual, intranasal/intratracheal, intravaginal, intrarectal), coupled with intramuscular SIV envelope boosting. Replicating Ad-GFP included in the regimen targeted and persisted in lung and rectal tissue monocyte/macrophages and mDCs regardless of immunization route. The ability of replicating Ad-recombinants to overcome restrictions imposed by the common mucosal immune system and target macrophages and professional APCs support their continued use. Macaques in all immunization groups developed SIV env-specific IgA antibodies in mucosal secretions. Notably, mucosal antibody titers were correlated with delayed SIVmac251 acquisition following repeated low-dose rectal challenges with a viral dilution that transmitted a single variant. These findings strengthen the concept that multiple immune mechanisms, cellular and innate as well as systemic and mucosal humoral immunity, should be exploited for optimal vaccine protection.
(C) 2012 Lippincott Williams & Wilkins, Inc.