Analysis of recombinant mycobacteria as T helper type 1 vaccines in an allergy challenge model

The potential for development of mycobacteria as T helper type 1 (Th1) vacc ines capable of induction of Th1 responses to recombinant antigens was expl ored in a model system based on an immunodominant peptide from house dust m ite. Different recombinant mycobacterial preparations were compared for the ir ability to induce a Th1 response to the peptide. It was found that mycob acterial viability was not a prerequisite for Th1 immunogenicity. A dominan t interferon-gamma (IFN-gamma) response to peptide was observed in splenocy tes from C57BL/6J mice immunized with live or heat-killed preparations of r ecombinant Mycobacterium vaccae or with live attenuated bacillus Calmette-G uerin (BCG) vaccine expressing the antigen. Interleukin-5 (IL-5), a marker of a Th2 response, was detected only in mice receiving live M. vaccae. A si milar pattern was observed in BALB/b mice, although the magnitude of the IF N-gamma response was much lower. Control and immunized mice were subsequent ly exposed to allergen using a Th2-inducing challenge protocol. A significa nt shift from a Th2 to a Th1 response was observed in immunized mice, as ju dged by cytokine expression by splenocytes and by subclass of circulating a ntibody. The effect was seen in three inbred mouse strains differing in the ir innate bias towards Th1 or Th2 responses. It was dependent on the presen ce of specific antigen in the mycobacterial preparation and, under the immu nization conditions tested, was more pronounced with dead M. vaccae than wi th live BCG as carrier vaccine. The results demonstrate the potency of kill ed mycobacteria as Th1 adjuvants and suggest a potential application for re combinant mycobacteria in antigen-specific immune modulation.