期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 2, 页码 385-392出版社
WILEY
DOI: 10.1002/eji.201141903
关键词
Infectious diseases; Memory cells; Tuberculosis; T cells; Vaccination
类别
资金
- NHMRC [570768]
- Rebecca L Cooper Medical Research Foundation
- Spanish Ministerio de Ciencia e Innovacion [BIO2008-01561]
- European NEWTBVAC [241745]
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.
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