IL-7-Adjuvanted Vaginal Vaccine Elicits Strong Mucosal Immune Responses in Non-Human Primates

Mucosal immune responses are crucial in protecting against pathogens entering through mucosal surfaces. However, due to poor T-cell responsiveness upon antigenic stimulation, immunity remains difficult obtain vaccines and requires appropriate adjuvants. We previously demonstrated that administered systemically healthy macaques or locally expressed the intestinal mucosa of acutely SIV-infected macaques, interleukin-7 (IL-7) triggers chemokine expression cell homing into mucosae, suggesting its important role development responses. therefore examined whether local delivery recombinant glycosylated simian IL-7 (rs-IL-7gly) vaginal rhesus could prepare lower female genital tract (FGT) for subsequent immunization act as an efficient adjuvant. First, we showed administration rs-IL-7gly overexpression chemokines infiltration mDCs, macrophages, NKs, B- T-cells lamina propria while MamuLa-DR + APCs accumulated epithelium. Subsequent anti-DT resulted a faster, stronger, more persistent antibody response compared DT-immunization alone. Indeed, detected robust productions DT-specific IgAs IgGs their secretions identified cells secreting draining lymph nodes. Finally, involved organization tertiary lymphoid structures (TLS) was only increased IL-7-adjuvanted immunized macaques. Interestingly, TLSs developed around PNAd high endothelial venules FGT sampled 2 weeks after last immunization. Non-traumatic prepares respond allows strong chemokine-dependent recruitment cells, activation mDCs formation TLSs. The localization IgA plasma upper argues contribution production specific immunoglobulins secretions. Our results highlight potential potent adjuvant stimulate system elicit immunization, which is most promising way confer protection many sexually transmitted diseases.