A new vaccine against tuberculosis shows greater protection in a mouse model with progressive pulmonary tuberculosis

Abstract

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.