Levine M M, Kaper J B, Herrington D, Ketley J, Losonsky G, Tacket C O, Tall B, Cryz S
Department of Medicine, University of Maryland School of Medicine, Baltimore.
Lancet. 1988 Aug 27;2(8609):467-70. doi: 10.1016/s0140-6736(88)90120-1.
The genes encoding the A (toxic) subunit of cholera toxin were deleted from pathogenic Vibrio cholerae O1 strain 569B by recombinant techniques, leaving intact production of immunogenic, non-toxic B subunit. The resultant strain, CVD 103, evaluated for safety, immunogenicity, and efficacy as a live oral vaccine, was highly attenuated and elicited strong antibacterial and antitoxic immune responses; a single dose significantly protected volunteers against challenge with pathogenic V cholerae O1 of either serotype or biotype. A further derivative, CVD 103-HgR, which has an Hg++-resistance gene to differentiate it from wild-type vibrios, was also well-tolerated, immunogenic, and protective; moreover, faecal excretion of this derivative was significantly lower than that of CVD 103, which should minimise environmental spread of the vaccine. CVD 103-HgR is a candidate for expanded clinical trials in endemic areas.
通过重组技术从致病性霍乱弧菌O1菌株569B中删除了编码霍乱毒素A（毒性）亚基的基因，使得免疫原性无毒B亚基的产生保持完整。对所得菌株CVD 103作为活口服疫苗的安全性、免疫原性和有效性进行了评估，该菌株高度减毒，并引发强烈的抗菌和抗毒免疫反应；单剂量就能显著保护志愿者免受任何血清型或生物型致病性霍乱弧菌O1的攻击。另一种衍生物CVD 103-HgR，具有Hg++抗性基因以使其与野生型弧菌区分开来，它也具有良好的耐受性、免疫原性和保护性；此外，该衍生物的粪便排泄量明显低于CVD 103，这应能最大程度减少疫苗在环境中的传播。CVD 103-HgR是在流行地区扩大临床试验的候选疫苗。
