Intranasal delivery of chitosan–DNA vaccine generates mucosal SIgA and anti-CVB3 protection

• DOI: 10.1016/j.vaccine.2004.03.033
• Publication Date: 2004-04-21T04:48:34Z
• Authors: Wei Xu; Yan Shen; Zhenggang Jiang; Ying Wang; Yiwei Chu; Sidong Xiong
• Keywords: Gene Expression Regulation, Viral; Male; Chitosan; Mice, Inbred BALB C; 0303 health sciences; Chemistry, Pharmaceutical; Myocardium; Coxsackievirus Infections; Enzyme-Linked Immunosorbent Assay; Viral Vaccines; Antibodies, Viral; Microspheres; Immunoglobulin A; 3. Good health; Mice; 03 medical and health sciences; Vaccines, DNA; Animals; Deoxyribonuclease I; Capsid Proteins; Administration, Intranasal; Enterovirus; Plasmids

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.