Oral immunization of mice with ricin toxoid vaccine encapsulated in polymeric microspheres against aerosol challenge.
Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50 microg of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49. With the short schedule a total of seven or six doses of 25 microg (lot #111) were administered on days 1, 2, 3, 14, 15, 16 and 30, or on 1, 2, 14, 15, 30, 31 and 32, respectively. Mice immunized orally with the long schedule, 50 microg of RT vaccine incorporated into poly-DL-lactide-co-glycolyde (DL-PLG) microspheres (MS) produced serum IgG, IgG2a and IgA ELISA antibodies. All mice immunized with RT in DL-PLG MS (RT-MS) were protected against a lethal ricin aerosol challenge. In contrast, with the same schedule and with the same dose, the aqueous vaccine (RT) failed to stimulate IgG, IgG2a and IgA antibodies, and these mice were not protected against an aerosol ricin toxin challenge. With the shorter immunization scheme, seven doses of 25 microg RT-MS stimulated a significant, though reduced, protection with the microencapsulated, but not with the aqueous vaccine. When the first and second 3-day cycles of the short immunization schedule was reduced to two doses, and the 3-day cycle was administered at the end of the schedule, neither RT-MS nor RT stimulated protection against the challenge. These results indicated that successful oral immunization with RT-MS depended on both the dose and the schedule, consisting of three consecutive days of administration in two cycles, 4 weeks apart. Altering this schedule and the dose, resulted in a reduced protection or no protection at all. Furthermore, under the conditions of this study, the advantage of the microencapsulated RT vaccine over the aqueous vaccine for effective oral immunization was well demonstrated.
Kende
Meir
M
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702-5011, USA. meir.kende@det.amedd.army.mil
Yan
Changhong
C
Hewetson
John
J
Frick
Matthew A
MA
Rill
Wayne L
WL
Tammariello
Ralph
R
D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D019344:Lactic Acid; D051379:Mice; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012276:Ricin / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D014121:Toxoids / Q000008:administration & dosage* / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology; D014867:Water
D000336:Aerosols; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011108:Polymers; D014121:Toxoids; D014612:Vaccines; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012276:Ricin