Intranasal delivery of chitosan-DNA vaccine generates mucosal SIgA and anti-CVB3 protection.
Coxsackievirus B3 infections are common causes of acute and chronic myocarditis with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce CVB3 specific immune responses. Intranasal administration with chitosan-DNA complex prepared by votexing DNA with chitosan, a natural mucus absorption enhancer, resulted in transgenic DNA expression in mouse nasopharynx. Mice immunized with chitosan-DNA (pcDNA3-VP1) encoding VP1, major structural protein of CVB3, produced much higher levels of serum IgG and mucosal secretory IgA compared to mice treated with pcDNA3-VP1 or pcDNA3. Increased virus-specific cytotoxic activity of spleen cells derived from chitosan-DNA vaccinated mice was also determined. Chitosan-pcDNA3-VP1 intranasal immunization resulted in 42.9% protection of mice against lethal CVB3 challenge and a significant reduction of viral load after acute CVB3 infection. Meanwhile no myonecrosis or infiltrating immune cells indicating ongoing myocarditis was detected in hearts of surviving mice treated with chitosan-DNA. Together, Our data show that intranasal delivery of chitosan-DNA vaccine successfully induced mucosal SIgA secretion and might be a promising vaccine candidate to protect against CVB3 infection.
Xu
Wei
W
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
Shen
Yan
Y
Jiang
Zhenggang
Z
Wang
Ying
Y
Chu
Yiwei
Y
Xiong
Sidong
S
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D036022:Capsid Proteins / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D048271:Chitosan; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003850:Deoxyribonuclease I / Q000737:chemistry; D004770:Enterovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015967:Gene Expression Regulation, Viral; D007070:Immunoglobulin A / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009206:Myocardium / Q000473:pathology; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use; D014765:Viral Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D001616:beta-Galactosidase / Q000096:biosynthesis
D000914:Antibodies, Viral; D036022:Capsid Proteins; D007070:Immunoglobulin A; D019444:Vaccines, DNA; D014765:Viral Vaccines; D048271:Chitosan; D003850:Deoxyribonuclease I; D001616:beta-Galactosidase