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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kou, Y; Xu, Y; Zhao, Z; Liu, J; Wu, Y; You, Q; Wang, L; Gao, F; Cai, L; Jiang, C

Published Date

  • October 2017

Published In

Volume / Issue

  • 190 /

Start / End Page

  • 51 - 57

PubMed ID

  • 28728855

Electronic International Standard Serial Number (EISSN)

  • 1879-0542

Digital Object Identifier (DOI)

  • 10.1016/j.imlet.2017.07.007


  • eng

Conference Location

  • Netherlands