Protection against VirulentMycobacterium aviumInfection following DNA Vaccination with the 35-Kilodalton Antigen Is Accompanied by Induction of Gamma Interferon-Secreting CD4+T Cells

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Abstract
Mycobacterium aviumis an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency ofM. aviuminfection is also increasing in the immunocompetent population. The antigen repertoire ofM. aviumvaries from that ofMycobacterium tuberculosis, with the immunodominant 35-kDa protein being present inM. aviumandMycobacterium lepraebut not in members of theM. tuberculosiscomplex. Here we show that a DNA vector encoding thisM. avium35-kDa antigen (DNA-35) induces protective immunity against virulentM. aviuminfection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-γ) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4+T-cell response, with an accumulation of CD4+CD44hiCD45RBloT cells and an increase in antigen-specific IFN-γ production. The protective effect of the DNA-35 vectors againstM. aviuminfection was comparable to that of vaccination withMycobacterium bovisBCG and significantly greater than that for previous treated infection withM. avium. These results illustrate the importance of the 35-kDa protein in the protective response toM. aviuminfection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronicM. aviuminfection.