Protective immunity afforded by attenuated, PhoP-deficient Mycobacterium tuberculosis is associated with sustained generation of CD4+ T-cell memory
✍ Scribed by Jonathan K. Nambiar; Rachel Pinto; Juan I. Aguilo; Kiyoshi Takatsu; Carlos Martin; Warwick J. Britton; James A. Triccas
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 364 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Definition of protective immunity induced by effective vaccines is important for the design of new pathogen control strategies. Inactivation of the PhoP response‐regulator in Mycobacterium tuberculosis results in a highly attenuated strain that demonstrates impressive protective efficacy in pre‐clinical models of tuberculosis. In this report we demonstrate that the protection afforded by the M. tuberculosis phoP mutant strain is associated with the long‐term maintenance of CD4^+^ T‐cell memory. Immunization of mice with SO2 resulted in enhanced expansion of M. tuberculosis‐specific CD4^+^ T cells compared with vaccination with the BCG vaccine, with an increased frequency of these cells persisting at extended time‐points after vaccination. Strikingly, vaccination with SO2 resulted in sustained generation of CD4^+^ T cells displaying a central memory phenotype, a property not shared by BCG. Further, SO2 vaccination markedly improved the generation of polyfunctional cytokine‐secreting CD4^+^ T cells compared with BCG vaccination. The improved generation of functionally competent memory T cells by SO2 correlated with augmented recall responses in SO2‐vaccinated animals after challenge with virulent M. tuberculosis. This study defines a mechanism for the protective effect of the SO2 vaccine and suggests that deletion of defined virulence networks may provide vaccine strains with potent immuno‐stimulatory properties.