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Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis.

Publication ,  Journal Article
Kou, Y; Xu, Y; Zhao, Z; Liu, J; Wu, Y; You, Q; Wang, L; Gao, F; Cai, L; Jiang, C
Published in: Immunol Lett
October 2017

Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines. To improve the immunogenicity of MVA-based vaccines, we introduced the tPA signal sequence in order to increase the antigen expression and secretion. Two recombinant MVA vectors expressing the Ag85B-TB10.4 fusion protein with or without tPA signal sequence were constructed and verified. Following the homologous prime-boost administration regimen in mice, levels of antigen-specific antibodies and cytokines (e.g., IFN-γ, TNF-α, IL-5, IL-6) and the percent of activated T cells were found to be significantly increased by the tPA signal sequence. However, the mean IgG2a/IgG1 ratios in the two recombinant MVA immunization groups were similar. Our present study demonstrated that the tPA signal sequence could enhance the immunogenicity of an MVA-based vaccine against TB without changing the balance of Th1 and Th2 immune responses. Thus, the tPA signal sequence may be applied to MVA-vector based vaccines for providing a better immune effect.

Duke Scholars

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Published In

Immunol Lett

DOI

EISSN

1879-0542

Publication Date

October 2017

Volume

190

Start / End Page

51 / 57

Location

Netherlands

Related Subject Headings

  • Viral Vaccines
  • Vaccinia virus
  • Vaccinia
  • Vaccines, Synthetic
  • Vaccines, DNA
  • Vaccination
  • Tuberculosis
  • Tissue Plasminogen Activator
  • T-Lymphocytes
  • Protein Sorting Signals
 

Citation

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Kou, Y., Xu, Y., Zhao, Z., Liu, J., Wu, Y., You, Q., … Jiang, C. (2017). Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis. Immunol Lett, 190, 51–57. https://doi.org/10.1016/j.imlet.2017.07.007
Kou, Yiming, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, and Chunlai Jiang. “Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis.Immunol Lett 190 (October 2017): 51–57. https://doi.org/10.1016/j.imlet.2017.07.007.
Kou Y, Xu Y, Zhao Z, Liu J, Wu Y, You Q, et al. Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis. Immunol Lett. 2017 Oct;190:51–7.
Kou, Yiming, et al. “Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis.Immunol Lett, vol. 190, Oct. 2017, pp. 51–57. Pubmed, doi:10.1016/j.imlet.2017.07.007.
Kou Y, Xu Y, Zhao Z, Liu J, Wu Y, You Q, Wang L, Gao F, Cai L, Jiang C. Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis. Immunol Lett. 2017 Oct;190:51–57.
Journal cover image

Published In

Immunol Lett

DOI

EISSN

1879-0542

Publication Date

October 2017

Volume

190

Start / End Page

51 / 57

Location

Netherlands

Related Subject Headings

  • Viral Vaccines
  • Vaccinia virus
  • Vaccinia
  • Vaccines, Synthetic
  • Vaccines, DNA
  • Vaccination
  • Tuberculosis
  • Tissue Plasminogen Activator
  • T-Lymphocytes
  • Protein Sorting Signals