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 Mycobacterium tuberculosis as well as in some non-tuberculous mycobacteria (NTM), such as M. kansasii. M. kansasii 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 alpha-galactosylceramide (alpha GC), a ligand of invariant NKT cells. We found that B cells loaded with alpha GC had increased levels of CD80 and CD86 after in vitro stimulation with NKT cells. Immunization of mice with B/alpha GC/vacESAT6 induced CD4(+) T cells producing TNF-alpha and IFN-gamma in response to heat-killed M. tuberculosis. Immunization of mice with B/alpha GC/vacESAT6 ameliorated severe lung inflammation caused by M. kansasii infection. We also confirmed that immunization with B/alpha GC/vacESAT6 reduced M. kansasii bacterial burden in the lungs. In addition, therapeutic administration of B/alpha GC/vacESAT6 increased IFN-gamma(+) CD4(+) T cells and inhibited the progression of lung pathology caused by M. kansasii infection. Thus, B/alpha GC/vacESAT6 could be a potent vaccine candidate for the prevention and treatment of ESAT6-expressing mycobacterial infection caused by M. kansasii.