Enhancement of Intranasal Vaccination in Mice with Deglycosylated Chain A Ricin by LTR72, a Novel Mucosal Adjuvant
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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Intranasal i.n. vaccination with two suboptimal doses of 8 microg 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 microg 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 12, 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 LD50 ricin toxin, while in the presence of 4, 2, and 1 microg LTR72, 100, 100 and 90 of the vaccinated mice survived, respectively. Safety of administration of two doses of LTR72 is indicated by the absence of histopathological changes in every organ including the lung and the CNS of the mice during the vaccination and during 57 days of the study.
- Medicine and Medical Research