Induction of secretory immunity with bioadhesive poly (D,L-lactide-co-glycolide) microparticles containing Streptococcus sobrinus glucosyltransferase

The effect of mucosal delivery of Streptococcus sobrinus glucosyltransferas e (GTF) in bioadhesive poly (D,L-lactide-co-glycolide) (PLGA) microparticle s on induction of salivary IgA and serum IgG antibody responses was measure d in Sprague-Dawley rats. Preparations of GTF/PLGA/gelatin microparticles, or PLGA/gelatin microparticles or GTF in alum, were administered four times at weekly intervals by intranasal or intragastric routes. Two subcutaneous injections of GTF in PLGA/gelatin microparticles or in alum were given to separate groups of rats. Significant elevations in salivary IgA antibody le vels to S. sobrinus GTF were observed only in the groups immunized intranas ally 28 days after immunizations were begun. Five of six rats given the GTF microparticles intranasally had positive salivary IgA antibody responses t o GTF, and the mean salivary IgA antibody level of this group was 30-fold h igher than any other mucosally or systemically immunized group. Salivary Ig A responses in the GTF-microparticle group remained significantly higher th an all other mucosally immunized groups for at least 10 weeks after the pri mary immunization. All rats in this group demonstrated aspects of anamnesis following a more limited secondary course of intranasal administration. In tranasal administration of GTF in microparticles also induced a serum IgG r esponse to GTF in some rats. After secondary intranasal GTF microparticle a dministration, several rats had sustained serum IBG antibody levels that we re within the range of sera from rats subcutaneously injected with GTF in m icroparticles or in alum. Thus intranasal delivery of GTF-containing bioadh esive microparticles induced the highest and longest lasting salivary immun e response of any mucosal or systemic route or vehicle tested and could be expected to be a useful method for induction of mucosal immunity.