The ΔfbpA attenuated candidate vaccine from Mycobacterium tuberculosis, H37Rv primes for a stronger T-bet dependent Th1 immunity in mice
| Autor: | Amanda K. Smith, Lisa Y. Armitige, Ashish Arora, Kimberly S. Schluns, Devin R. Lindsey, Akshay Meher, Chinnaswamy Jagannath, Cherie Michelle Roche |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Microbiology (medical) Hydrolases T cell Immunology Colony Count Microbial chemical and pharmacologic phenomena Biology Vaccines Attenuated CXCR3 complex mixtures Microbiology Article Mycobacterium tuberculosis Mice Antigen medicine Animals Tuberculosis Tuberculosis Vaccines Antigens Bacterial CFP-10 hemic and immune systems Dendritic Cells Th1 Cells biology.organism_classification Virology Coculture Techniques Mice Inbred C57BL Disease Models Animal Infectious Diseases medicine.anatomical_structure ESAT-6 BCG Vaccine T-Box Domain Proteins Tuberculosis vaccines BCG vaccine Acyltransferases |
| Zdroj: | Tuberculosis. 91:S96-S104 |
| ISSN: | 1472-9792 |
| DOI: | 10.1016/j.tube.2011.10.018 |
| Popis: | The ΔfbpA candidate vaccine derived from Mycobacterium tuberculosis (H37Rv) (Mtb) protects mice better than BCG against tuberculosis, and we investigated the hypothesis that ΔfbpA may induce a stronger Th1 immunity. Since T-bet transcription factor regulates Th1 immunity, mice infected with ΔfbpA, BCG vaccine and related mycobacteria were analyzed for T-bet positive T cells. Mouse dendritic cells (DCs) or macrophages were also pulsed with excretory-secreted antigens (ES; Antigen-85B, ESAT-6 and CFP10) and cocultured with T cells from immunized or naïve mice and tested for in vitro induction of T-bet and IFN-γ. In both models, ΔfbpA mutant induced a stronger response of T-bet(+)CD4 T cells, which correlated with an increased expansion of IFN-γ(+)CD4 T cells in vivo and in vitro. When DCs pulsed with ES antigens were allowed to stimulate T cells, ESAT-6 and CFP-10 failed to induce a recall expansion of T-bet(+)IFN-γ(+)CD4 T cells from BCG vaccinated mice. Thus, deletion of RD1 in BCG seems to reduce its ability to induce T-bet and induce stronger Th1 immunity. Finally, mice were vaccinated with ΔfbpA and BCG and challenged with virulent Mtb for evaluation of protection and T cell expansion. ΔfbpA vaccinated mice showed a rapid and stronger expansion of CD4(+)CXCR3(+) IFN-γ(+) T cells in the lungs of Mtb challenged mice, compared to those which had BCG vaccine. ΔfbpA immunized mice also showed a better decline of the Mtb bacterial counts of the lungs. Mtb derived ΔfbpA candidate vaccine therefore induces qualitatively better T-bet dependent Th1 immunity than BCG vaccine. |
| Databáze: | OpenAIRE |
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