B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases

Abstract

Early secretory antigenic target-6 (ESAT6) is a potent immunogenic antigen expressed in <i>Mycobacterium tuberculosis</i> as well as in some non-tuberculous mycobacteria (NTM), such as <i>M. kansasii</i>. <i>M. kansasii</i> is one of the most clinically relevant species of NTM that causes mycobacterial lung disease, which is clinically indistinguishable from tuberculosis. In the current study, we designed a novel cell-based vaccine using B cells that were transduced with vaccinia virus expressing ESAT6 (vacESAT6), and presenting α-galactosylceramide (αGC), a ligand of invariant NKT cells. We found that B cells loaded with αGC had increased levels of CD80 and CD86 after <i>in vitro</i> stimulation with NKT cells. Immunization of mice with B/αGC/vacESAT6 induced CD4⁺ T cells producing TNF-α and IFN-γ in response to heat-killed <i>M. tuberculosis</i>. Immunization of mice with B/αGC/vacESAT6 ameliorated severe lung inflammation caused by <i>M. kansasii</i> infection. We also confirmed that immunization with B/αGC/vacESAT6 reduced <i>M. kansasii</i> bacterial burden in the lungs. In addition, therapeutic administration of B/αGC/vacESAT6 increased IFN-γ⁺ CD4⁺ T cells and inhibited the progression of lung pathology caused by <i>M. kansasii</i> infection. Thus, B/αGC/vacESAT6 could be a potent vaccine candidate for the prevention and treatment of ESAT6-expressing mycobacterial infection caused by <i>M. kansasii</i>.