Enhanced mucosal and systemic immune responses to a vaginal vaccine coadministered with RANTES-expressing plasmid DNA using in situ-gelling mucoadhesive delivery system

Abstract

To develop more potent and convenient mucosal vaccines, we investigated the effect of an in situ-gelling mucoadhesive vaginal vaccine delivery system and a genetic chemokine adjuvant on the local and systemic immune responses. The in situ-gelling mucoadhesive delivery system of hepatitis B surface antigen (HBsAg), composed of poloxamers and polycarbophil, showed the prolonged retention at the vaginal tissues. Following intravaginal administration to mice, HBsAg-specific IgA was induced in the vagina and saliva, and IgG was produced in the serum. RANTES-expressing plasmid (pRANTES) intravaginally coadministered with HBsAg showed the expression at the vaginal tissues, and more effectively induced the vaginal IgA and serum IgG immune responses than did cholera toxin (CT). The intramuscular coadministration of pRANTES with HBsAg also increased both serum IgG levels and mucosal IgA levels. Regardless of the adjuvants, the in situ-gelling mucoadhesive HBsAg delivery system enhanced the mucosal and systemic immune responses. At 42 days after the first immunization, the highest vaginal IgA levels were induced after intravaginal immunization of HBsAg plus pRANTES using the in situ-gelling mucoadhesive delivery system, showing 182- and 1035-fold higher titer compared to the groups receiving HBsAg alone in PBS by intravaginal and intramuscular routes, respectively. Our results indicate that the use of in situ-gelling mucoadhesive delivery systems with the genetic chemokine adjuvant pRANTES would be advantageous for more effective induction of mucosal and systemic immune responses to intravaginally administered vaccines.