IMMUNOGENICITY AND EFFICACY OF A TUBERCULOSIS DNA VACCINE ENCODING THE COMPONENTS OF THE SECRETED ANTIGEN-85 COMPLEX

BALB/c and C57BL/6 mice were injected intramuscularly with plasmid DNA encoding the three components of the immunodominant 30-32 kDa antigen 85 complex (Ag85A, Ag85B, and Ag85C) from Mycobacterium tuberculosis culture filtrate, in order to investigate the utility of nucleic acid vaccination for induction of immune responses against mycobacterial an tigens. Ag85A and Ag85B encoding plasmids induced a robust Th1-like re sponse towards native Ag85, characterized by elevated levels of interl eukin (IL)-2, interferon-gamma, and TNF-alpha. Levels of IL-4, IL-6, a nd IL-10 were low or undetectable. Plasmid encoding Ag85C was not effe ctive. Cytotoxic T cell activity was also generated in in vitro restim ulated splenocyte cultures from Ag85A and Ag85B DNA vaccinated mice. F inally, Ag85A and Ag85B DNA vaccination conferred significant protecti on against mycobacterial replication in lungs from B6 mice, subsequent ly challenged. Therefore, this technique may be useful for the definit ion of protective antigens of M. tuberculosis and the development of a more effective tuberculosis vaccine. (C) 1997 Elsevier Science Ltd.