Immunogenicity and efficacy of a tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex

Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

“…Moreover, mouse immunization experiments have shown that vaccination with DNA encoding Ag85A could generate strong CD4 + T-cell-mediated Th1 and CD8 + T-cell-mediated CTL responses and be responsible for improved protection against challenge by virulent M. tuberculosis in animal models. [15][16][17] In the present study, we demonstrate for the first time that Ag85A DNA vaccine could also be effective at reducing the reactivation of established M. tuberculosis (Table 1 and Figure 4). Rates of reactivation in both lungs and spleens were found to be inversely correlated with the Ag85A-specific IFN-g production level, but not with the CFspecific IFN-g level (Figures 3a and b), indicating that Ag85A-specific Th1 immunity may be more important than Th1 immune response specific for CF in terms of protection against M. tuberculosis reactivation.…”

“…Prophylactic DNA vaccines expressing M. tuberculosis antigens or cytokines are of particular interest, because of their efficiency and long-lasting effect in animal TB models. For example, prophylactic DNA vaccines expressing various M. tuberculosis antigens, including Ag85A, [15][16][17] Ag85B, 17,18 65 kDa heat shock protein, 19,20 and PstS-3 21 , were found to be effective at limiting the growth of M. tuberculosis in mice. In contrast, there has been little evidence that DNA vaccines are useful as therapeutic vaccines against TB.…”

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

“…Running the ESAT-6 sequence through the SYFPEITHI database [29] predicted a 9-mer CD8 epitope restricted by H2-D b (residues 17-25; AIQGNVTSI). This peptide was recognized by the same frequency of IFN-c-producing CD8 cells as ESAT-6 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (data not shown). In addition, a CD4 epitope localized to residues 241-255 of Ag85B as well as a subdominant CD8 epitope located in residues 61-82 were found after vaccination with the adenovirus-based vaccine ( Fig.…”

“…Recognition of ESAT-6 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and Ag85B 241-255 during infection with M. tuberculosis…”

“…The two components in this fusion protein are secreted antigen, recognized strongly during TB infection [21,22], and with a documented track record as protective antigens in TB animal models [23][24][25]. Both antigens are known to contain multiple T cell epitopes [26,27], and some of these epitopes have been shown to promote high levels of protective immunity when administered singly as vaccines in animal models [23].…”