title: Generation of protective immune responses against coxsackievirus B3 challenge by DNA prime-protein boost vaccination.
abstract: Coxsackievirus B3 (CVB3) causes viral myocarditis and can ultimately result in dilated cardiomyopathy. However, there is no vaccine available for clinical use. In this study, we assessed the protection provided by three immunization strategies against CVB3 infection. Vaccination was performed with a DNA vaccine expressing the cloned capsid gene VP1 or a vaccine developed from purified VP1 protein. Third, a strategy of vaccination was attempted with the DNA vaccine followed by two boosts with the recombinant protein vaccine (DNA prime-protein boost vaccine). Followed immunization, mice were challenged with CVB3 infection. Improved induction of CVB3-specific antibodies and neutralizing antibodies were found in mice immunized by the DNA prime-protein boost regimen. Furthermore, virus-specific cytotoxic activity of spleen cells derived from DNA prime-protein boost vaccinated mice was elicited. In addition, the DNA prime-protein boost vaccine resulted in protection of 75% of mice from lethal CVB3 challenge and a significant reduction of viral load in sera of immunized mice after acute CVB3 infection. There was a significant reduction in myonecrosis and infiltrating myocardial immune cells indicating reduced severity of myocarditis in surviving mice. These findings demonstrated that a DNA prime-protein boost immunization strategy, but not a DNA vaccine or protein vaccine alone, was effective in eliciting both humoral and cell-mediated immune responses against CVB3 infection in mice and might be a promising vaccine candidate.
authors.affiliation: Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017, PR China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Lan
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Gao
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.forename: Xia
authors.initials: X
authors.lastname: Chuai
authors.forename: Yuhuai
authors.initials: Y
authors.lastname: Jin
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Xian
authors.initials: X
authors.lastname: Xian
authors.forename: Guixia
authors.initials: G
authors.lastname: Liu
authors.forename: Lixin
authors.initials: L
authors.lastname: Xie
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000517:prevention & control*; D004247:DNA / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D019562:Viral Load / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D007106:Immune Sera; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D004247:DNA