INTRANASAL STIMULATION OF LONG-LASTING IMMUNITY AGAINST AEROSOL RICINCHALLENGE WITH RICIN TOXOID VACCINE ENCAPSULATED IN POLYMERIC MICROSPHERES

Intranasal (i.n.) immunization with ricin toxoid (RT) vaccine encapsul ated in poly(lactide-co-glycolide) microspheres (RT-PLG-Ms) and poly(L -lactide) microspheres (RT-PLA-Ms) stimulated systemic and mucosal imm une response and protected mice from aerosolized ricin intoxication. H igh titers of anti-ricin IgG2a were stimulated in serum of mice with o ne or two doses of RT-Ms 6 weeks postimmunization. However, in the lun gs, no IgG2a or total IgG was elicited either with RT-Ms or with aqueo us RT. At 6 weeks postimmunization, a single dose of the RT-Ms stimula ted secretory IgA (sIgA) in the lungs of four of six mice, but a secon d immunizing dose did not enhance the stimulation. A single dose of aq ueous RT vaccine failed to stimulate sIgA in the lungs, while, a secon d dose induced sIgA in 50% of the mice. One or two i.n. doses of RT-Ms protected most of the mice against lethal aerosol-delivered ricin tox in 6 weeks post-immunization. In contrast, protection was absent or ma rginal after one or two doses of aqueous RT vaccine. In both studies, the protection against lethal aerosol challenge was significantly bett er with one dose of RT-Ms than with two doses of aqueous vaccine, whic h may be attributed to the induction of sIgA in the lungs and the seru m. Duration of the IgG2a and IgA in the serum, particularly that of Ig G2a was much longer after the administration of RT-Ms than after the a queous vaccine. The geometric mean IgG2a titers stimulated with two do ses of RT-Ms remained high during 40 weeks postimmunization and were u p to 25 times higher than the titers induced with aqueous RT vaccine. After 6 weeks, the IgG2a induced by two doses of aqueous vaccine was n o longer detectable. Persistence of antibody response was predictive o f efficacy. At 1 year postimmunization with two doses of RT-Ms, 100% o f mice protected against lethal ricin challenge. However, at the same time no protection was afforded by two doses of aqueous RT. The result s of the present study consistently demonstrated the advantages of mic roencapsulated RT vaccine to stimulate effective and long-lasting prot ection by i.n. administration.