title: A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 enhances cell-mediated immune response and longevity of the total IgG to influenza A virus M2e protein in mice.
abstract: As the importance of virus-specific IgG2a and strong induction of Th1 type immune response for virus clearance was reported, conventional influenza vaccines induce a highly humoral immune response and fail to induce cytotoxic T-lymphocyte (CTL) immunity. Hence, in agreement with heat shock protein 70 (HSP70) acting as Th1 cytokine-like adjuvant, an Escherichia coli-expressed r4M2e.HSP70c fusion protein comprising C-terminus of Mycobacterium tuberculosis HSP70 genetically fused to four tandem repeats of influenza A virus M2e was constructed. Then, the case-control study was carried out to evaluate the humoral and cellular responses elicited against M2e in Balb/C mice by intramuscular immunization with r4M2e.HSP70c alone. Our results showed that r4M2e.HSP70c rather than control groups, r4M2e, r4M2e+Alum, or rHSP70c, significantly elevated both longevity and serum level of the total M2e-specific IgG antibody, induced a Th1 skewed humoral and cellular immune responses, increased the level of IFN-γ in BALF, and promoted the proliferation of peripheral blood lymphocytes. Furthermore, a virus challenge experiment revealed that mice vaccinated with r4M2e.HSP70c limited the severity of influenza A disease by 100% survival rate, less sever body weight loss and delaying the onset of morbidity in mice for 2days rather than other control groups. Here, we used r4M2e.HSP70c to stimulate M2e-specific antibody and cellular immune responses in Balb/C mice. The mHSP70c in the fusion form induced a long lasting Th1 skewed humoral and cellular immune responses against its associated protein. It seems anti-M2e antibodies limit viral replication and ameliorate influenza infection that allows the immune system to induce sterilizing HA-antibody against whole virion that leads to full protection against virulent influenza infection.
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651, Tehran, Iran; Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran, Iran.
authors.forename: Mehran
authors.initials: M
authors.lastname: Dabaghian
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651, Tehran, Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Latifi
authors.affiliation: Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), P.O. Box 31975/148, Karaj, Tehran, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Tebianian
authors.affiliation: Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), P.O. Box 31975/148, Karaj, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Dabaghian
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651, Tehran, Iran. Electronic address: smebrahimi@shirazu.ac.ir.
authors.forename: Seyyed Mahmoud
authors.initials: SM
authors.lastname: Ebrahimi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007371:Interferon-gamma; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: HSP70; Immune response; Influenza; M2e; Vaccine