SETTING: The effectiveness of Bacillus Calmette-Guerin (BCG) vaccination in reducing tuberculosis (TB) prevalence rates is poor, resulting in urgent need for improved immunization programs, with new and more effective vaccines against TB. OBJECTIVE: To develop a recombinant Tice BCG vaccine against TB that overexpresses the 38-kDa antigen of Mycobacterium tuberculosis in order to protect against infection by M. tuberculosis H37Rv and hyper-virulent M. tuberculosis Beijing genotype. DESIGN: M. tuberculosis 38-kDa protein was cloned into a mycobacterial shuttle plasmid, which was used to overexpress the 38 kDa protein in BCG Tice to produce the recombinant vaccine, rBCG38 Tice (rBCG38). RESULTS: Compared with BCG Tice, which conferred little protection against the Beijing strain of M. tuberculosis, vaccination with the rBCG38 increased survival of mice infected with either M. tuberculosis H37Rv or a Beijing strain of M. tuberculosis, isolate 9501000. Vaccination with either BCG Tice or rBCG38 resulted in enhanced protection against mycobacterial growth in lung tissue by reducing the number of colony-forming units (CFU). The vaccine induced a strong and highly significant Th1 response, shown by the high level of IL-2 and IFN-gamma cytokine producer cells found in the lungs of challenged mice, and an increase in the IgG2a:IgG1 ratio found in the pooled sera of the vaccinated mice. CONCLUSIONS: This study showed that rBCG38 vaccine induced a strong Th1 response, demonstrated by the high levels of IL-2 and IFN-gamma producer cells and IgG2a. Protection was mediated for as long as 6 and 4 months after challenge with M. tuberculosis H37Rv and Beijing genotypes, respectively.
SETTING: The effectiveness of Bacillus Calmette-Guerin (BCG) vaccination in reducing tuberculosis (TB) prevalence rates is poor, resulting in urgent need for improved immunization programs, with new and more effective vaccines against TB. OBJECTIVE: To develop a recombinant Tice BCG vaccine against TB that overexpresses the 38-kDa antigen of Mycobacterium tuberculosis in order to protect against infection by M. tuberculosis H37Rv and hyper-virulent M. tuberculosis Beijing genotype. DESIGN:M. tuberculosis 38-kDa protein was cloned into a mycobacterial shuttle plasmid, which was used to overexpress the 38 kDa protein in BCG Tice to produce the recombinant vaccine, rBCG38 Tice (rBCG38). RESULTS: Compared with BCG Tice, which conferred little protection against the Beijing strain of M. tuberculosis, vaccination with the rBCG38 increased survival of mice infected with either M. tuberculosis H37Rv or a Beijing strain of M. tuberculosis, isolate 9501000. Vaccination with either BCG Tice or rBCG38 resulted in enhanced protection against mycobacterial growth in lung tissue by reducing the number of colony-forming units (CFU). The vaccine induced a strong and highly significant Th1 response, shown by the high level of IL-2 and IFN-gamma cytokine producer cells found in the lungs of challenged mice, and an increase in the IgG2a:IgG1 ratio found in the pooled sera of the vaccinated mice. CONCLUSIONS: This study showed that rBCG38 vaccine induced a strong Th1 response, demonstrated by the high levels of IL-2 and IFN-gamma producer cells and IgG2a. Protection was mediated for as long as 6 and 4 months after challenge with M. tuberculosis H37Rv and Beijing genotypes, respectively.
Authors: Julio C C Lorenzi; Ana P F Trombone; Carolina D Rocha; Luciana P Almeida; Ricardo L Lousada; Thiago Malardo; Isabela C Fontoura; Renata A M Rossetti; Ana F Gembre; Aristóbolo M Silva; Celio L Silva; Arlete A M Coelho-Castelo Journal: BMC Biotechnol Date: 2010-10-20 Impact factor: 2.563
Authors: Suraj B Sable; Mani Cheruvu; Subhadra Nandakumar; Sunita Sharma; Kakali Bandyopadhyay; Kathryn L Kellar; James E Posey; Bonnie B Plikaytis; Rama Rao Amara; Thomas M Shinnick Journal: PLoS One Date: 2011-07-25 Impact factor: 3.240
Authors: Maroeska J Burggraaf; Louis S Ates; Alexander Speer; Kim van der Kuij; Coen Kuijl; Wilbert Bitter Journal: Microb Cell Fact Date: 2019-03-06 Impact factor: 5.328