Enhancement of Intranasal Vaccination in Mice with Deglycosylated Chain A Ricin by LTR72, a Novel Mucosal Adjuvant

摘要

Intranasal (i.n.) vaccination with two sub-optimal doses of 8 micro- grams of deglycosylated chain A ricin (DGCA) stimulated low anti-ricin ELISA IgG and neutralizing antibody responses, and the vaccine was only marginally protective against a lethal ricin toxin aerosol challenge. However, in the presence of 4, 2, or 1 micro-gram of the mucosal adjuvant LTR72, a mutant of the heat-labile enterotoxin of Escherichia coli, the low antibody response and protection were substantially enhanced. In comparison to the vaccination with DGCA alone, vaccination with DGCA in the presence of three dose levels of LTR72, the anti-ricin ELISA serum IgG geometric mean titer (GMT) was increased, respectively, 191-, 572-, and 51-fold for IgG; 91-, 93-, and 60-fold for IgG1; nine-, six-, and two-fold for IgG2a; zero-, two-, and zero-fold for IgA. The three dose levels of the adjuvant enhanced the anti-ricin ELISA immunoglobulin GMTs in the lung lavage 4-, 14-, and 7-fold for IgG; two-, five-, and six-fold for IgG1; two-, six-, and two-fold IgG2a; and zero-, three-, and zero-fold for IgA, respectively. Compared to GMT obtained with the aqueous vaccine (1:2), the 10% serum neutralizing antibody GMT for the three dose levels was enhanced 25-, 60-, and 62-fold, respectively while the 50% neutralizing antibody GMT was enhanced more than 3-, 19- and 10-fold. Only 20% of the mice immunized with DGCA survived the lethal whole body aerosol challenge with 5-10 LD(50) ricin toxin, while in the presence of 4, 2, and 1 micro-gram LTR72, 100, 100 and 90% of the vaccinated mice survived, respectively.