APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice

Verfasser / Beitragende:
[Saman Soleimanpour, Hadi Farsiani, Arman Mosavat, Kiarash Ghazvini, Mohammad Eydgahi, Mojtaba Sankian, Hamid Sadeghian, Zahra Meshkat, Seyed Rezaee]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/24(2015-12-01), 10467-10480
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00253-015-6952-z  |2 doi 
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245 0 0 |a APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice  |h [Elektronische Daten]  |c [Saman Soleimanpour, Hadi Farsiani, Arman Mosavat, Kiarash Ghazvini, Mohammad Eydgahi, Mojtaba Sankian, Hamid Sadeghian, Zahra Meshkat, Seyed Rezaee] 
520 3 |a Numerous studies have demonstrated that targeting immunogens to FcγR on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fcγ2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fcγ2a (ESAT6:HspX:mFcγ2a) or 6× His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose-6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Guérin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-γ secretion from splenic cells; the Fc-tagged subunit vaccine induced a more effective Th1 immune response (IFN-γ, 910pg/mL, and IL-12, 854pg/mL) with a very low increase in IL-17 (∼0.1pg/mL) and IL-4 (37pg/mL) and a mild increase in TGF-β (543pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-γ to ESAT6:HspX:Fcγ2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fcγ2a used as a delivery vehicle supported the idea of selective uptake, inducing cross-presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Tuberculosis  |2 nationallicence 
690 7 |a APC-targeting  |2 nationallicence 
690 7 |a Fc-fusion vaccine  |2 nationallicence 
690 7 |a ESAT-6  |2 nationallicence 
690 7 |a HspX  |2 nationallicence 
700 1 |a Soleimanpour  |D Saman  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Farsiani  |D Hadi  |u Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran  |4 aut 
700 1 |a Mosavat  |D Arman  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Ghazvini  |D Kiarash  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Eydgahi  |D Mohammad  |u Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran  |4 aut 
700 1 |a Sankian  |D Mojtaba  |u Immunobiochemistry Lab, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Sadeghian  |D Hamid  |u Organic Chemistry, Department of Laboratory Sciences, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Meshkat  |D Zahra  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
700 1 |a Rezaee  |D Seyed  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/24(2015-12-01), 10467-10480  |x 0175-7598  |q 99:24<10467  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-015-6952-z  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6952-z  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Soleimanpour  |D Saman  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Farsiani  |D Hadi  |u Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Mosavat  |D Arman  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ghazvini  |D Kiarash  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Eydgahi  |D Mohammad  |u Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sankian  |D Mojtaba  |u Immunobiochemistry Lab, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sadeghian  |D Hamid  |u Organic Chemistry, Department of Laboratory Sciences, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Meshkat  |D Zahra  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Rezaee  |D Seyed  |u Microbiology & Virology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/24(2015-12-01), 10467-10480  |x 0175-7598  |q 99:24<10467  |1 2015  |2 99  |o 253