title: Fc-based delivery system enhances immunogenicity of a tuberculosis subunit vaccine candidate consisting of the ESAT-6:CFP-10 complex.
abstract: Tuberculosis (TB) remains a major global health threat despite chemotherapy and Bacilli Calmette-Guérin (BCG) vaccination. Therefore, a safer and more effective vaccine against TB is urgently needed. This study evaluated the immunogenicity of a recombinant fusion protein consisting of early secreted antigenic target protein 6 kDa (ESAT-6), culture filtrate protein 10 kDa (CFP-10) and the Fc-domain of mouse IgG2a as a novel subunit vaccine. The recombinant expression vectors (pPICZαA-ESAT-6:CFP-10:Fcγ2a and pPICZαA-ESAT-6:CFP-10:His) were transferred into Pichia pastoris. After SDS-PAGE and immunoblotting, the immunogenicity of the recombinant proteins was evaluated in mice. When both recombinant proteins (ESAT-6:CFP-10:Fcγ2a and ESAT-6:CFP-10:His) were used for vaccination, Th1-type cellular responses were induced producing high levels of IFN-γ and IL-12. However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a small increase in IL-4 as compared to the BCG and ESAT-6:CFP-10:His groups. Moreover, mice primed with BCG and then supplemented with ESAT-6:CFP-10:Fcγ2a produced the highest levels of IFN-γ and IL-12 in immunized groups. The findings indicate that when Fcγ2a is fused to the ESAT-6:CFP-10 complex, as a delivery vehicle, there could be an increase in the immunogenicity of this type of subunit vaccine. Therefore, additional investigations are necessary for the development of appropriate Fc-based tuberculosis vaccines.
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Farsiani
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Arman
authors.initials: A
authors.lastname: Mosavat
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Saman
authors.initials: S
authors.lastname: Soleimanpour
authors.affiliation: Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Sadeghian
authors.affiliation: Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Akbari Eydgahi
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Ghazvini
authors.affiliation: Immunobiochemistry Lab, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Sankian
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Aryan
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Saeid Amel
authors.initials: SA
authors.lastname: Jamehdar
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Medical School, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, Iran. RezaeeR@mums.ac.ir.
authors.forename: Seyed Abdolrahim
authors.initials: SA
authors.lastname: Rezaee
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007114:Immunization; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit