PROTECTIVE IMMUNITY AGAINST SALMONELLA-TYPHIMURIUM ELICITED IN MICE BY ORAL VACCINATION WITH PHOSPHORYLCHOLINE ENCAPSULATED IN POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES

Encapsulation of vaccines in biodegradable microspheres provides excel lent mucosal immunogens with a high potential for immunization against bacterial infections, We tested the protective immunity elicited by i ntragastric vaccination with phosphorylcholine (PC) encapsulated in po ly(DL-lactide-co-glycolide) (DL-PLG) microspheres against Salmonella t yphimurium in a mouse model of invasive intestinal infection, We chose PC as the antigen because it was found to elicit an immune response a fter intestinal exposure of mice to PC-bearing S, typhimurium and beca use anti-PC immunity protects mice against Streptococcus pneumoniae, a nother PC-bearing microorganism, Mice were primed intragastrically on days 1, 2, and 3 and boosted on days 28, 29, and 30 with PC (280 mu g) coupled to porcine thyroglobulin (PC-thyr) encapsulated in DL-PLG mic rospheres, free PC-thyr, or blank microspheres. A significant rise in anti-PC immunoglobulin A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed in the intestinal secretions after immunization with PC-loaded microspheres, compared to the titers of mi ce immunized with free PC-thyr or blank microspheres, This antibody re sponse peaked 14 days after the last boost and correlated with a highl y significant resistance to oral challenge by S, typhimurium C5 (P < 1 0(-3)), Control mice were primed intraperitoneally on day 1 with 15 mu g of PC in complete Freund's adjuvant and boosted on days 10, 14, and 20) with the same dose without adjuvant but via the same route, In th ese mice, the levels of anti-PC IgA in intestinal secretions were equi valent to those of the mice intragastrically immunized with PC-loaded microspheres, but protection was significantly weaker, suggesting that either the IgAs were not functional or that other immune mechanisms a re important in protection, Taken together, our results highlight the potential of antigen encapsulation in DL-PLG microspheres for elicitin g protective immunity against invasive intestinal bacterial diseases a nd suggest that a similar strategy could be used against diseases caus ed by other PC-bearing microorganisms.