EVALUATION OF A UDP-GLUCOSE-4-EPIMERASELESS MUTANT OF SALMONELLA-TYPHI AS A LIVE ORAL VACCINE
EVALUATION OF A UDP-GLUCOSE-4-EPIMERASELESS MUTANT OF SALMONELLA-TYPHI AS A LIVE ORAL VACCINE
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DOI：
10.1093/infdis/136.6.717
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发表时间：
1977-01-01
影响因子：
6.4
通讯作者：
LIBONATI, JP
中科院分区：
文献类型：
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作者：
GILMAN, RH;HORNICK, RB;LIBONATI, JP
伤寒沙门氏菌的突变体 (Ty21a) 缺乏 UDP 葡萄糖-4-差向异构酶，在志愿者中进行了评估，将其用作减毒口服伤寒疫苗。 155 名男性接种了 5 至 8 剂疫苗（每剂含有 3-1010 个活生物体），没有出现明显副作用。疫苗株在粪便中的排泄率较低，大部分隔离发生在接种后第 1 天。在测试的 958 个粪便分离株中均未发现能够发酵半乳糖的回复突变体。突变株 Ty21a 在含有 0.1% 半乳糖的脑心浸液肉汤 (BHIB) 中生长，与不含半乳糖的相同疫苗株相比，产生更多的 O 侧链。与对照组相比，志愿者接种了在半乳糖中生长的 Ty21a 菌株，然后用 105 株强毒伤寒沙门氏菌攻击，可显着预防疾病，并且粪便中携带的伤寒沙门氏菌也减少。与对照相比，在没有半乳糖的情况下生长的菌株 Ty21a 没有为疫苗接种者提供显着的保护，也没有减少伤寒沙门氏菌的粪便排泄。 Ty21a 菌株在含有 0.1% 半乳糖的 BHIB 中生长时，会产生一种安全、稳定和具有保护性的口服疫苗，值得在现场试验中进行进一步研究。
A mutant (Ty21a) of S. typhi, which lacks the enzyme UDP glucose-4-epimerase, was evaluated in volunteers for use as a live attenuated oral typhoid vaccine. Five to 8 doses of vaccine (containing 3-1010 viable organisms/dose) were given to 155 men without significant side effects. The rate of excretion of the vaccine strain in stools was low and the majority of isolations occurred on day 1 after vaccination. Revertants able to ferment galactose were not found in any of 958 stool isolates tested. The mutant, strain Ty21a, grown in brain-heart infusion broth (BHIB) with 0.1% galactose, produces more O side chain than the same vaccine strain cultivated without galactose. Volunteers vaccinated with strain Ty21a grown in galactose and then challenged with 105 virulent S. typhi were significantly protected from disease and also had decreased stool carriage of S. typhi as compared with controls. Strain Ty21a grown without galactose did not provide vaccinees significant protection nor decrease fecal excretion of S. typhi as compared with controls. Strain Ty21a, when grown in BHIB with 0.1% galactose, results in a safe, stable and protective oral vaccine that warrants further study in field trials.