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• W2066751520 endingPage "395" @default.
• W2066751520 startingPage "387" @default.
• W2066751520 abstract "•Protection can be improved by supplementing instead of boosting BCG immune responses. •T cell responses not detectable by IFN-γ assays can enhance TB control. •Improving central memory T cell responses by vaccines prolongs TB control. •TB virulence and latency antigens missing from BCG improve vaccine effect. •Vaccine-induced Th17 responses enhance early control of TB. The vaccine discovery paradigm in tuberculosis (TB) has been to mimic the natural immune response to infection. With an emphasis on interferon (IFN)-γ as the main protective cytokine, researchers have selected dominant antigens and administered them in delivery systems to promote strong T helper (Th)1 responses. However, the Bacillus Calmette–Guérin (BCG) vaccine is a strong inducer of Th1 cells, yet has limited protection in adults, and further boosting by the Modified-Vaccinia-Ankara (MVA)85A vaccine failed to enhance efficacy in a clinical trial. We review the current understanding of host–pathogen interactions in TB infection and propose that rather than boosting Th1 responses, we should focus on understanding protective immune responses that are lacking or insufficiently promoted by BCG that can intervene at critical stages of the TB life cycle. The vaccine discovery paradigm in tuberculosis (TB) has been to mimic the natural immune response to infection. With an emphasis on interferon (IFN)-γ as the main protective cytokine, researchers have selected dominant antigens and administered them in delivery systems to promote strong T helper (Th)1 responses. However, the Bacillus Calmette–Guérin (BCG) vaccine is a strong inducer of Th1 cells, yet has limited protection in adults, and further boosting by the Modified-Vaccinia-Ankara (MVA)85A vaccine failed to enhance efficacy in a clinical trial. We review the current understanding of host–pathogen interactions in TB infection and propose that rather than boosting Th1 responses, we should focus on understanding protective immune responses that are lacking or insufficiently promoted by BCG that can intervene at critical stages of the TB life cycle." @default.
• W2066751520 created "2016-06-24" @default.
• W2066751520 creator A5022168346 @default.
• W2066751520 creator A5090428914 @default.
• W2066751520 date "2014-08-01" @default.
• W2066751520 modified "2023-09-23" @default.
• W2066751520 title "Tuberculosis vaccines – rethinking the current paradigm" @default.
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