The mast cell activator Compound 48/80 is a potent adjuvant for intradermally-administered anthrax protective antigen. (41.12)

Recent studies have reported that mast cells play a role in the trafficking of dendritic cells and lymphocytes to lymph nodes draining sites of infection. To test the hypothesis that mast cell activators could be used as vaccine adjuvants, C3H/HeN mice were intradermally vaccinated in the ear on days 0 & 21 with 0.5 μg recombinant anthrax protective antigen (rPA) alone or combined with 30 μg compound 48/80 (C 48/80), a mast cell activator. CpG oligodeoxynucleotide (CpG ODN, 1 μg) was used as a control. Ear swelling was monitored 24 hours after immunization to measure injection site inflammation. Mice immunized with rPA alone had an average ear thickness (mm) of 0.0059 while mice immunized with rPA + C 48/80 had an ear thickness of 0.0426 (p < 0.001 vs rPA alone). Mice immunized with rPA + CpG ODN had an ear thickness of 0.1519 (p < 0.001 vs rPA), significantly greater than swelling induced by C 48/80 (p < 0.001). Day 42 serum from mice immunized with PA alone had serum anti-PA IgG titers of 1:27,238 while mice immunized with PA + C 48/80 had anti-PA titers of 1:10,568,984 (p < .001 vs PA alone). Similar titers were detected in mice vaccinated with rPA plus CpG ODN. Antibodies induced with rPA + C 48/80 neutralized anthrax lethal toxin. Our findings suggest that mast cell activators provide effective vaccine adjuvant activity when delivered intradermally while inducing less injection site inflammation than CpG ODN.