Protection against virulent Mycobacterium avium infection following DNA vaccination with the 35-kilodalton antigen is accompanied by induction of gamma interferon-secreting CD4(+) T cells

Mycobacterium avium is an opportunistic pathogen that primarily infects imm unocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of,il. avium varies from that of Mycobacterium tuberculosis, with the immun odominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this il I. avium 35-kDa antigen (DNA-35) induces protectiv e immunity against virulent M. avium infection, and this protective effect persists over 13 weeks of infection. In C57BL/6 mice, DNA vaccines expressi ng the 35-kDa protein as a cytoplasmic or secreted protein, both induced st rong T-cell gamma interferon (IFN-gamma) and humoral immune responses, Furt hermore, the antibody response was to conformational determinants, confirmi ng that the vector-encoded protein had adopted the native conformation, DNA -35 immunization resulted in an increased activated/memory CD4(+) T-cell re sponse, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and an i ncrease in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vac cination with Mycobacterium bovis BCG and significantly greater than that f or previous treated infection with M. avium. These results illustrate the i mportance of the 35-kDa protein in the protective response to M. avium infe ction and indicate that DNA vaccination successfully promotes a sustained l ever of protection during chronic M. avium infection.