Xu Wei, Shen Yan, Chen Rui-zhen, Xiong Si-dong
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Zhonghua Yi Xue Za Zhi. 2004 Feb 17;84(4):334-8.
To enhance the effect of chitosan-pcDNA3-VP1 DNA vaccine to prevent onset of coxsackievirus B3 (CVB3)-induced myocarditis.
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.
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.
Novel chitosan-pcDNA3-VP1-HApLys16 vaccine containing "endosome fusogenic peptide" could more effectively prevent CVB3-induced myocarditis than chitosan-pcDNA3-VP1 vaccine.
增强壳聚糖 - pcDNA3 - VP1 DNA疫苗预防柯萨奇病毒B3（CVB3）诱导的心肌炎发病的效果。
合成含有“内体融合肽”的HA - pLys16“载体肽”和聚赖氨酸，并依次与DNA和壳聚糖复合，得到壳聚糖 - pcDNA3 - VP1 - HApLys16疫苗。以200μg pcDNA3 - VP1的总剂量给予BALB/c小鼠。3周后用3倍半数致死量（LD50）的CVB3感染小鼠以诱导心肌炎。观察并比较体重减轻、体心比、外观及心脏组织的HE染色情况，以此作为心肌炎严重程度的指标。
壳聚糖 - pcDNA3 - VP1 - HApLys16疫苗经鼻内免疫可增强黏膜sIgA的分泌。在3倍LD50的CVB3感染后，pcDNA3免疫的小鼠组在CVB3感染后体重减轻5.75%，而壳聚糖 - pcDNA3 - VP1和壳聚糖 - pcDNA3 - VP1 - HApLys16免疫的小鼠体重分别增加了1.75%和5.44%。壳聚糖 - pcDNA3 - VP1 - HAplys16组的体心比达到193.77，提示心肌炎减轻。壳聚糖 - pcDNA3 - VP1 - HAplys16免疫的小鼠心脏中未见心肌坏死或免疫细胞浸润，壳聚糖 - pcDNA3 - VP1免疫的小鼠发病率为1/6，心肌炎非常轻微。而pcDNA3免疫的小鼠发病率为6/6，心肌炎极其严重。pcDNA3免疫的小鼠心脏比正常的大，有许多白色条纹，壳聚糖 - pcDNA3 - VP1和壳聚糖 - pcDNA3 - VP1 - HApLys16免疫的小鼠心脏中未观察到这种情况。
含有 “内体融合肽” 的新型壳聚糖 - pcDNA3 - VP1 - HApLys16疫苗比壳聚糖 - pcDNA3 - VP1疫苗能更有效地预防CVB3诱导的心肌炎。
