title: Mucosal co-immunization with AIM2 enhances protective SIgA response and increases prophylactic efficacy of chitosan-DNA vaccine against coxsackievirus B3-induced myocarditis.
abstract: Coxsackievirus B3 (CVB3) infection is considered as the most common cause of viral myocarditis with no available vaccine. Considering that CVB3 mainly invades through the gastrointestinal mucosa, the development of CVB3-specific mucosal vaccine, which is the most efficient way to induce mucosal immune responses, gains more and more attention. In this study, we used absent in melanoma 2 (AIM2) as a mucosal adjuvant to enhance the immunogenicity and immunoprotection of CVB3-specific chitosan-pVP1 vaccine. Mice were intranasally co-immunized with 50 μg chitosan-pAIM2 and equal amount of chitosan-pVP1 vaccine 4 times at 2 week-intervals, and then challenged with CVB3 2 weeks after the last immunization. Compared with chitosan-pVP1 vaccine immunization alone, chitosan-pAIM2 co-immunization enhanced resistance to CVB3-induced myocarditis evidenced by significantly enhanced ejection fractions from 55.40 ± 9.35 to 80.31 ± 11.35, improved myocarditis scores from 1.50 ± 0.45 to 0.30 ± 0.15, reduced viral load from 3.33 ± 0.50 to 0.50 ± 0.65, and increased survival rate from 40.0% to 75.5%. This increased immunoprotection might be attributed to the augmented level of CVB3-specific fecal SIgA with high affinity and neutralizing ability. In addition, co-immunization with chitosan-pAIM2 remarkably facilitated dendritic cells (DCs) recruitment to mesenteric lymph nodes (MLN), and promoted the expression of IgA-inducing factors (BAFF, APRIL, iNOS, RALDH1, IL-6, TGF-β), which might account for its mucosal adjuvant effect. This strategy may represent a promising prophylactic vaccine against CVB3-induced myocarditis.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity; Institutes of Biology and Medical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Dafei
authors.initials: D
authors.lastname: Chai
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity; Institutes of Biology and Medical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity; Institutes of Biology and Medical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity; Institutes of Biology and Medical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity; Institutes of Biology and Medical Sciences; Soochow University; Suzhou, PR China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000276:immunology*; D029822:Enterovirus B, Human; D006367:HeLa Cells; D006801:Humans; D007114:Immunization / Q000379:methods; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C540422:Aim2 protein, mouse; D004268:DNA-Binding Proteins; D007071:Immunoglobulin A, Secretory; D019444:Vaccines, DNA; D048271:Chitosan
keywords: AIM2; Coxsackievirus B3; SlgA; adjuvant; chitosan; mucosal vaccine; viral myocarditis