[A novel DNA vaccine containing endosome-fusogenic peptide prevents CVB3-induced myocarditis in mice].
OBJECTIVE
To enhance the effect of chitosan-pcDNA3-VP1 DNA vaccine to prevent onset of coxsackievirus B3 (CVB3)-induced myocarditis.


METHODS
HA-pLys16 "carrier peptide" containing "endosome fusogenic peptide" and poly-Lysine was synthesized and complexed with DNA and chitosan sequentially, resulting chitosan-pcDNA3-VP1-HApLys16 vaccine. It was administrated to BALB/c mice with a total dose of 200 micro g pcDNA3-VP1. Mice were infected with 3 (LD(50) CVB3 3 weeks later to induce myocarditis. Loss of body weight, body/heart weight ratio, outlook and HE staining of heart tissues was observed and compared as an indicative of severity of myocarditis.


RESULTS
chitosan-pcDNA3-VP1-HApLys16 vaccine intranasal immunization enhanced secretion of mucosal sIgA. After 3 x LD(50) CVB3 infection, pcDNA3 immunized mice groups lost their 5.75% weight following CVB3 infection, while chitosan-pcDNA3-VP1 and chitosan-pcDNA3-VP1-HApLys16 immunized mice increased their body weight by 1.75% and 5.44%. Body/heart weight ratio of chitosan-pcDNA3-VP1-HAplys16 group reached 193.77 suggesting lightened myocarditis. No myonecrosis or infiltrating immune cells existed in heart of chitosan-pcDNA3-VP1-HAplys16 immunized mice, and 1/6 of incidence and very light myocarditis were seen in chitosan-pcDNA3-VP1 immunized mice. While in pcDNA3 immunized mice 6/6 incidence and extremely severe myocarditis were observed. Heart from pcDNA3-immunized mice was bigger than normal ones and had a lot of white stripes, which were not observed in that of chitosan-pcDNA3-VP1 and chitosan-pcDNA3-VP1-HApLys16 immunized mice.


CONCLUSIONS
Novel chitosan-pcDNA3-VP1-HApLys16 vaccine containing "endosome fusogenic peptide" could more effectively prevent CVB3-induced myocarditis than chitosan-pcDNA3-VP1 vaccine.
Xu
Wei
W
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Shen
Yan
Y
Chen
Rui-zhen
RZ
Xiong
Si-dong
SD
D000818:Animals; D003384:Coxsackievirus Infections / Q000150:complications*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology; D005243:Feces / Q000737:chemistry; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000627:therapeutic use*
D007071:Immunoglobulin A, Secretory; D019444:Vaccines, DNA