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

Castañon-Arreola M, López-Vidal Y, Espitia-Pinzón C, Hernández-Pando R

Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico.

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.

Published 2 February 2005 in Tuberculosis (Edinb), 85(1): 115-26.
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