| The current anthrax vaccine available in the United States is prepared from the culture filtrate from a non-encapsulated, toxigenic strain of Bacillus anthracis. The vaccination regimen requires six intramuscular injections over a period of 18 months and induces primarily systemic but not mucosal immunity. An alternative anthrax vaccine composed of recombinant protein would be more easily standardized and would be free of potentially reactogenic cell wall components. In addition, an alternative vaccine which requires fewer doses, induces both systemic and mucosal immunity, or is administered via non-parenteral routes would be a significant improvement over the current anthrax vaccine. This study examined the effects of antigen dosage, type of adjuvant, number of immunizations, and route of administration on the development of an immune response to recombinant protective antigen (rPA) of B. anthracis. Increasing antigen dosage did not have a significant effect on the magnitude, quality, or duration of the immune response regardless of the type of adjuvant used. Mutated E. coli heat labile enterotoxin (mLT) adjuvant elicited a balanced immune response in vaccinated animals and induced a stronger humoral response that did the Type 1 adjuvant CpG. CpG-vaccinated mice which received three doses of vaccine developed significantly higher levels of antigen-specific serum antibody than did groups which received only two doses. In contrast, two doses of rPA plus mLT adjuvant induced the highest statistically significant levels of antigen-specific rPA antibody in vaccinated mice. The immune response in animals which received a priming dose consisting of a subcutaneous injection with alum adjuvant was primarily Type 2 and was not capable of modulation via heterologous boosting. In contrast, the immune response in animals primed mucosally with either adjuvant was susceptible to modulation when the route, adjuvant, or both were changed. Protective immunity against an encapsulated, toxin-positive strain of B. anthracis was not achieved in the C5-deficient A/J mouse strain using vaccine formulations based solely on the protective antigen protein. |
