title: A DNA vaccine-encoded nucleoprotein of influenza virus fails to induce cellular immune responses in a diabetic mouse model.
abstract: Influenza virus infections cause yearly epidemics and are a major cause of lower respiratory tract illnesses in humans worldwide. Influenza virus has long been recognized to be associated with higher morbidity and mortality in diabetic patients. Vaccination is an effective tool to prevent influenza virus infection in this group of patients. Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines. Internal highly conserved viral nucleoprotein (NP) can be delivered as a DNA vaccine to provide heterosubtypic immunity, offering resistance against various influenza virus strains. In this study, we investigated the efficacy of an NP DNA vaccine for induction of cell-mediated immune responses and protection against influenza virus infection in a mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized on days 0, 14, and 28 by injection of NP DNA vaccine. Two weeks after the last immunization, the cellular immune response was evaluated by gamma interferon (IFN-gamma), lymphocyte proliferation, and cytotoxicity assays. The mice were challenged with influenza virus, and the viral titers in the lungs were measured on day 4. Diabetic mice showed significantly smaller amounts of IFN-gamma production, lymphocyte proliferation, and cytotoxicity responses than nondiabetic mice. Furthermore, higher titers of the influenza virus were detected after challenge in the lungs of the diabetic mice. The present data suggest that the NP DNA vaccine with the protocol of immunization described here is not able to induce efficient cellular immune responses against influenza virus infection in diabetic mice.
authors.affiliation: Department of Virology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Jamali
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Sabahi
authors.forename: Taravat
authors.initials: T
authors.lastname: Bamdad
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Hashemi
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Mahboudi
authors.forename: Masume Tavasoti
authors.initials: MT
authors.lastname: Kheiri
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000276:immunology*; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007117:Immunization, Secondary / Q000379:methods; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000821:virology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D007371:Interferon-gamma