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Construction and immunogenicity of a new Fc-based subunit vaccine candidate against Mycobacterium tuberculosis

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Abstract

As an ancient disease, tuberculosis (TB) is a major global health threat. Therefore, there is an urgent need for an effective and safe anti-TB vaccine. In the current study, a delivery system of Fc domain of mouse IgG2a and early secreted antigenic target protein 6 (ESAT-6) was evaluated for the selective uptake of antigens by antigen-presenting cells (APCs). Thus, it was based on the immunogenicity of a fusion protein. The study was initiated by the transfer of recombinant expression vectors of pPICZαA-ESAT-6:Fcγ2a and pPICZαA-ESAT-6: His into Pichia pastoris (P. pastoris). Recombinant proteins were assessed for immunogenicity following the immunoblotting analysis. High levels of IFN-γ and IL-12 were produced to induce Th1-type cellular responses through vaccination with both recombinant proteins [ESAT-6:Fcγ2a (EF) and ESAT-6:His (EH)]. The Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low increment in IL-4 compared to PBS, BCG, and EH groups. Although in all the immunized groups, the ratio of IFN-γ/IL-4 was in favor of Th1 responses, the highest Th1/Th2 balance was observed in EF immunized group. Fc fragment of mouse IgG2a may induce a selective uptake of APCs towards the cross-presentation and formation of Th1 responses in favor of an appropriate protective anti-tuberculosis reaction. Thus, further research on Fc-fusion proteins is required to develop Fc-based TB vaccines.

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Acknowledgments

This study has been supported by vice chancellor for research of Mashhad University of Medical Sciences (Grant no. 910072). This study was a part of a PhD dissertation by Abdollah Kebriaei.

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Authors and Affiliations

  1. Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Abdollah Kebriaei, Mohammad Derakhshan, Zahra Meshkat, Hadi Farsiani, Arman Mosavat, Saman Soleimanpour & Kiarash Ghazvini

  2. Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Abdollah Kebriaei, Mohammad Derakhshan, Zahra Meshkat, Hadi Farsiani, Arman Mosavat, Saman Soleimanpour & Kiarash Ghazvini

  3. Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Mohammad Reza Akbari Eidgahi

  4. Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Abdolrahim Rezaee

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  1. Abdollah Kebriaei
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  2. Mohammad Derakhshan
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Correspondence to Kiarash Ghazvini.

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Kebriaei, A., Derakhshan, M., Meshkat, Z. et al. Construction and immunogenicity of a new Fc-based subunit vaccine candidate against Mycobacterium tuberculosis . Mol Biol Rep 43, 911–922 (2016). https://doi.org/10.1007/s11033-016-4024-9

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