Heterologous prime-boost vaccination against tuberculosis with recombinant Sendai virus and DNA vaccines

  • Zhidong Hu
  • Weimin Jiang
  • Ling Gu
  • Dan Qiao
  • Tsugumine Shu
  • Douglas B. Lowrie
  • Shui-Hua LuEmail author
  • Xiao-Yong FanEmail author
Original Article


In an earlier study, a novel Sendai virus–vectored anti-tuberculosis vaccine encoding Ag85A and Ag85B (SeV85AB) was constructed and shown to elicit antigen-specific T cell responses and protection against Mycobacterium tuberculosis (Mtb) infection in a murine model. In this study, we evaluate whether the immune responses induced by this novel vaccine might be elevated by a recombinant DNA vaccine expressing the same antigen in a heterologous prime-boost vaccination strategy. The results showed that both SeV85AB prime-DNA boost (SeV85AB-DNA) and DNA prime-SeV85AB boost (DNA-SeV85AB) vaccination strategies significantly enhanced the antigen-specific T cell responses induced by the separate vaccines. The SeV85AB-DNA immunization regimen induced higher levels of recall T cell responses after Mtb infection and conferred better immune protection compared with DNA-SeV85AB or a single immunization. Collectively, our study lends strong evidence that a DNA vaccine boost might be included in a novel SeV85AB immunization strategy designed to enhance the immune protection against Mtb.

Key messages

  • A heterologous prime-boost regimen with a novel recombinant SeV85AB and a DNA vaccine increase the T cell responses above those from a single vaccine.

  • The heterologous prime-boost regimen provided protection against Mtb infection.

  • The DNA vaccine might be included in a novel SeV85AB immunization strategy designed to enhance the immune protection against Mtb.


Tuberculosis Sendai virus DNA vaccine Prime-boost T cell responses 


Funding information

This work was supported by grants from Chinese National Mega Science and Technology Program on Infectious Diseases (2018ZX10731301, 2018ZX10302301), the National Natural and Science Foundation of China (31771004, 81873884, 81501365, 81601735, 81770011), and the Shanghai Science and Technology Commission (19XD1403100, 17ZR1423900).

Compliance with ethical standards

Conflict of interest

X.Y.F., T.S., Z.D.H., and D.B.L. are co-inventors on an SeV85AB vaccine patent application.

All animal experiments were approved by the Institutional Animal Care and Use Committee and were performed according to the guidelines of the Laboratory Animal Ethical Board of Shanghai Public Health Clinical Center.

Supplementary material

109_2019_1844_Fig7_ESM.png (423 kb)
Fig. 7

The gating strategy of IFN-γ, IL-2 and TNF-α staining. Representative flow cytometric dot plots are shown. CD4+ T cells were gated as CD3+CD4+ cells and CD8+ T cells were defined as CD3+CD4- cells. The expression of IFN-γ, IL-2 and TNF-α was determined by using appropriate antibodies and gated by respective isotype control staining. (PNG 423 kb)

109_2019_1844_MOESM1_ESM.tif (1.6 mb)
High Resolution (TIF 1597 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Zhidong Hu
    • 1
  • Weimin Jiang
    • 2
  • Ling Gu
    • 1
    • 3
    • 4
  • Dan Qiao
    • 5
  • Tsugumine Shu
    • 6
  • Douglas B. Lowrie
    • 1
    • 4
  • Shui-Hua Lu
    • 1
    • 3
    • 4
    Email author
  • Xiao-Yong Fan
    • 3
    • 4
    Email author
  1. 1.Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOHFudan UniversityShanghaiChina
  2. 2.Departments of Infectious Diseases, Huashan HospitalFudan UniversityShanghaiChina
  3. 3.School of Laboratory Medicine and Life ScienceWenzhou Medical UniversityWenzhouChina
  4. 4.TB CenterShanghai Emerging and Re-emerging InstituteShanghaiChina
  5. 5.Ruijin Hospital (North)Shanghai Jiaotong UniversityShanghaiChina
  6. 6.ID PharmaIbarakiJapan

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