An attenuated Salmonella-vectored vaccine elicits protective immunity against Mycobacterium tuberculosis.
There is a need to develop protective vaccines against tuberculosis (TB) that elicit full immune responses including mucosal immunity. Here, a live attenuated Salmonellatyphimurium aroA SL7207 vector TB vaccine, namely SL(E6-85B), harboring the Mycobacterium tuberculosis (M. tb) H37Rv ESAT6-Ag85B fusion gene was developed. The experimental data demonstrated that this SL(E6-85B) vaccine, or when it is combined with BCG vaccination, induced the strongest TB Ag-specific mucosal, humoral, and cellular immune responses comprised of increased proliferation of T cells, IFN-gamma expression, granzyme B production, as well as the greatest IFN-gamma production of effector-memory T (T(EM)) or effector CD8(+) T cell responses and exerted high protective efficacy in mice against virulent M. tb H37Rv challenge compared to the other vaccinated groups (mice immunized with SL(Ag85B), a DNA vaccine or BCG only). This strategy may represent a novel promising mucosal vaccine candidate for the prevention of TB which are inexpensive to produce, efficacious, and able to be given orally rather than by injection.
Wang
Qi-long
QL
Department of Immunology, Wuhan University School of Medicine, Wuhan 430071, People's Republic of China.
Pan
Qin
Q
Ma
Yunfeng
Y
Wang
Kun
K
Sun
Ping
P
Liu
Shengwu
S
Zhang
Xiao-Lian
XL
D000217:Acyltransferases / Q000276:immunology; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis; D053804:Granzymes