title: Construction and immunogenicity of a new Fc-based subunit vaccine candidate against Mycobacterium tuberculosis.
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.
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Abdollah
authors.initials: A
authors.lastname: Kebriaei
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Derakhshan
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Meshkat
authors.affiliation: Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Mohammad Reza Akbari
authors.initials: MR
authors.lastname: Eidgahi
authors.affiliation: Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Abdolrahim
authors.initials: SA
authors.lastname: Rezaee
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Microbiology and Virology, School of Medicine, 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.|Department of Microbiology and Virology, School of Medicine, 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.|Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Saman
authors.initials: S
authors.lastname: Soleimanpour
authors.affiliation: Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran. ghazvinik@mums.ac.ir.|Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. ghazvinik@mums.ac.ir.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Ghazvini
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010843:Pichia; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: ESAT-6; Fc domain; Immunogenicity; Mycobacterium tuberculosis; Subunit vaccine; Tuberculosis