摘要
霍乱是世界烈性传染病,由革兰氏阴性的霍乱弧菌引起,世界第7次大流行自1961年延续至今。波及五大洲100多个国家,尚未得到有效控制,且于1992年出现了新的血清型流行株,表明全球急需有效的霍乱疫苗。霍乱疫苗的免疫接种已有100多年历史,免疫效果不理想,仅能有短期保护作用。通过近十多年的研究。尤其是基因工程重组 DNA 技术的应用,已研制出一些新的霍乱疫苗:(1)BS/WS 灭活疫苗。由无毒的霍乱毒素 B 亚单位及杀死的全菌细胞组成,经场地试验验证是安全有效的.63 498人服苗后,在最初6个月保护效果为85%,免疫后3年为51%,且对预防旅行者腹泻也有短期效果(3个月),保护率达67%以上。(2)CVD103-HgR 减毒活疫苗。为减毒的霍乱活菌苗,首次免疫后即能产生保护的免疫反应,志愿者攻击试验对经典型保护率为82%-100%,对 Eltor 保护率62%-67%,免疫后仅4%试验者产生轻度腹泻,在印度尼西亚正在进行68 000人的场地试验。(3)沙门氏菌载体疫苗。将编码霍乱 O 抗原基因导入减毒的沙门氏菌载体疫苗株,构建伤寒/霍乱双价疫苗,经志愿者攻毒试验,对霍乱能产生25%保护率,引入霍乱弧菌其它保护性抗原基因以增强免疫效果的实验也在进行中。
Cholera is known as a worldwide deadly contagion caused by the gram negative hacteria Vi- bro cholerae,which has been spreading over five continents and more than one hundred countries involved. Since the 7^(th) worldwide epidemic from 1961,it has not been efficiently controlled yet.Cholera vaccines are in an urgent need in the world. The inoculation of cholera vaccine has been carried out for more than one hundred years,however,it only caused a short-term protection.New types of cholera vaccine via oral using the recombinant techniques have been prepared in the recent decade.(1)BS/WC Vaccine:it consists of nontoxic B subunit of cholera toxin and inactivated Vibrio whole cells.BS/WC Vaccine has little adverse reactions,and has been found completely safe by field trial.This oral vaccine,given to 63 498 people,provided 85% efficacy for 3 years. It can also prevent the travelers form diarrhea for a short period of time(3 months)with a protective efficacy of more than 67%.(2)CVD103-HgR:it is a live attenuated,oral cholera vaccine.The immune response could be produced after one dose.The protective efficacy for classical strain was 82%-100%,and 62%-67% for Eltor,when volunteers were challenged with fully enterotoxigenic wild-type of V.cholerae.Only 4% of vol- unteers had mild diarrhea after immunization.68 000 people field trial is being treated in Indonesia.(3)Sal- monella carder vaccine:a bivalent vaccine of typhi/cholera has been constructed by introducing the gene coding for the cholera O antigen to an attenuated vaccine strain of Salmonella carrier.In the volunteer chal- lenge model,the protective efficacy for choleara was 25%.The studies for enhancing the immune effect of cholera are underway by introduction of genes coding for the other protective antigens.