INDUCTION OF ANTIGEN-SPECIFIC ANTIBODIES IN VAGINAL SECRETIONS BY USING A NONTOXIC MUTANT OF HSAI-LABILE ENTEROTOXIN AS A MUCOSAL ADJUVANT

Immunization of the female reproductive tract is important for protect ion against sexually transmitted diseases and other pathogens of tile reproductive tract, However, intravaginal immunization with soluble an tigens generally does not induce high levels of secretory immunoglobul in A (IgA). We recently developed safe mucosal adjuvants by geneticall y detoxifying Escherichia coli heat-labile enterotoxin, a molecule wit h a strong mucosal adjuvant activity, and here we describe the use of the nontoxic mutant LTK63 to induce a response in the mouse vagina aga inst ovalbumin (Ova). The compared intravaginal and intranasal routes of immunization for induction of systemic and vaginal responses agains t LTK63 and Ova. We found that LTK63 is a potent mucosal immunogen whe n given by either the intravaginal or intranasal route. It induces a s trong systemic antibody response and IgG and long-lasting IgA in the v agina. The appearance of vaginal IgA is delayed in the intranasally im munized mice, hut the levels of vaginal anti-LTK63 IgA after repeated immunizations a:re higher in the intranasally immunized mise than in t he intravaginally immunized mice, LTK63 also acts as a mucosal adjuvan t, inducing a serum response against Ova, when given by both the intra vaginal and intranasal routes. However, vaginal IgA against Ova is sti mulated more efficiently when LTK63 and antigen ape given intranasally , in conclusion, our results demonstrate that LTK63 call be used as a mucosal adjuvant to induce antigen-specific antibodies in vaginal secr etions and show that the intranasal route of immunization is the most effective for this purpose.