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.
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
Wei
W
Xu
Yan
Y
Shen
Zhenggang
Z
Jiang
Ying
Y
Wang
Yiwei
Y
Chu
Sidong
S
Xiong
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