Differential Immune Responses and Protective Effects in Avirulent Mycobacterial Strains Vaccinated BALB/c Mice

Abstract

Screening live mycobacterial vaccine candidates is the important strategy to develop new vaccines against adult tuberculosis (TB). In this study, the immunogenicity and protective efficacy of several avirulent mycobacterial strains including Mycobacterium smegmatis, M. vaccae, M. terrae, M. phlei, M. trivial, and M. tuberculosis H37Ra were compared with M. bovis BCG in BALB/c mice. Our results demonstrated that differential immune responses were induced in different mycobacterial species vaccinated mice. As BCG-vaccinated mice did, M. terrae immunization resulted in Th1-type responses in the lung, as well as splenocytes secreting IFN-γ against a highly conserved mycobacterial antigen Ag85A. M. smegmatis also induced the same splenocytes secreting IFN-γ as BCG and M. terrae did. In addition, M. terrae and M. smegmatis-immunized mice predominantly increased expression of IL-10 and TGF-β in the lung. Most importantly, mice vaccinated with H37Ra and M. vaccae could provide the same protection in the lung against virulent M. tuberculosis challenge as BCG. The result may have important implications in developing adult TB vaccine.

Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

“…A selection of avirulent mycobacteria strains: M. smegmatis, M. vaccae, M. terrae, M. phlei, M. triviale, and M. tb H37Ra, were compared to BCG in mice. As expected, different immune responses were induced with the various mycobacterial species [55]. More importantly, subcutaneous vaccination with each strain was also able to control M. tb H37Rv infection to different degrees in mice.…”

“…Four weeks post infection, BCG, M. smegmatis, M. vaccae, and M. tb H37Ra provided the best protection with the lowest lung bacterial loads compared to unvaccinated mice (p < 0.01) [55]. In addition, M. terrae and M. triviale also provided some protection compared to unvaccinated mice (p < 0.05) [55]. While the mechanisms of these avirulent strains' protective immune responses require further study, these results may indicate a greater role for them in developing novel TB vaccines.…”

“…More importantly, subcutaneous vaccination with each strain was also able to control M. tb H37Rv infection to different degrees in mice. Four weeks post infection, BCG, M. smegmatis, M. vaccae, and M. tb H37Ra provided the best protection with the lowest lung bacterial loads compared to unvaccinated mice (p < 0.01) [55]. In addition, M. terrae and M. triviale also provided some protection compared to unvaccinated mice (p < 0.05) [55].…”

“…The mechanism of BCG's protective effect to M. tb infection could, in part, be due to cross-protection induced by shared antigens. With more than 150 known mycobacteria species, there is potential for another live avirulent strain that can also provide protection to M. tb via cross-protection [55]. A selection of avirulent mycobacteria strains: M. smegmatis, M. vaccae, M. terrae, M. phlei, M. triviale, and M. tb H37Ra, were compared to BCG in mice.…”

A New Adjuvant MTOM Mediates Mycobacterium tuberculosis Subunit Vaccine to Enhance Th1-Type T Cell Immune Responses and IL-2+ T Cells

“…In our earlier work, mouse immunization with live Mv strains induced protective immune responses against M. tb (20). In order to improve the adjuvant effect of MTO, we first incorporated heat-killed Mv in MTO to construct a new adjuvant, MTOM.…”