Tuberculosis DNA vaccine encoding Ag85A is immunogenic and protective whenadministered by intramuscular needle injection but not by epidermal gene gun bombardment

Immunogenicity and protective efficacy of a DNA vaccine encoding Ag85A from Mycobacterium tuberculosis were compared in BALB/c and C57BL (B6 and B10) mice immunized by intramuscular (i.m.) needle injection or epidermal gene g un (gg) bombardment. In BALB/c mice, gg immunization could induce elevated antibody and cytotoxic T lymphocyte responses with plasmid doses 50-fold lo wer than those required for i.m. immunization. Interleukin-2 (IL-2) and gam ma interferon (IFN-gamma) secretion, however, was much lower in gg-immunize d than in i.m.-immunized BALB/c mice. On the other hand, C57BL mice reacted only very weakly to gg immunization, whereas elevated Ag85A-specific antib ody, IL-2, and IFN-gamma responses (significantly higher than in BALB/c mic e) were detected following vaccination by the i.m. route. Antibody isotypes were indicative of Th2 activation following gg injection of BALB/c and of Th1 activation following i.m, injection of C57BL mice. Finally, C57BL but n ot BALB/c mice were protected by i.m. Ag85A DNA immunization against intrav enous At tuberculosis challenge, as measured by reduced numbers of CFU in s pleen and lungs, compared to animals vaccinated with control DNA, Gene gun immunization was not effective in either BALB/c or C57BL mice. These result s indicate that i.m. DNA vaccination is the method of choice for the induct ion of protective Th1 type immune responses with the Ag85A tuberculosis DNA vaccine.