一种营养缺陷型活口服福氏志贺菌疫苗：研发与测试

An auxotrophic live oral Shigella flexneri vaccine: development and testing.

作者信息

Kärnell A, Stocker B A, Katakura S, Sweiha H, Reinholt F P, Cam P D, Trach D D, Lindberg A A

机构信息

Department of Clinical Bacteriology, Clinical Research Center, Huddinge Hospital, Sweden.

出版信息

Rev Infect Dis. 1991 Mar-Apr;13 Suppl 4:S357-61. doi: 10.1093/clinids/13.supplement_4.s357.

DOI:10.1093/clinids/13.supplement_4.s357

PMID:2047663

Abstract

Through transduction, a wild-type strain of Shigella flexneri serotype Y (SFL1) was rendered auxotrophic and dependent on aromatic metabolites that are not available in mammalian tissues. Monkeys that were orally vaccinated with 10(11) bacteria of the transductant strain SFL114 remained healthy when challenged with 10(11) bacteria of wild-type strains of S. flexneri serotypes Y, 1b, and 2a. The safety and immunogenicity of SFL114 were next studied in volunteers who were given either 10(9) or 10(10) SFL114 bacteria orally. Mild intestinal discomfort that lasted for 1-2 days was reported by three (12%) of 25 volunteers given 10(9) live SFL114 bacteria and by 13 (54%) of 24 volunteers given 10(10) live SFL114 bacteria. A local intestinal secretory IgA response to the S. flexneri O-antigen was recorded. The in vitro and in vivo results suggest that the aroD transductant SFL114 possesses properties that are desirable in an oral live candidate vaccine.

摘要

通过转导，弗氏志贺菌血清型Y野生型菌株（SFL1）变成了营养缺陷型，依赖于哺乳动物组织中不存在的芳香族代谢物。用10¹¹转导菌株SFL114的细菌口服接种的猴子，在用10¹¹弗氏志贺菌血清型Y、1b和2a野生型菌株的细菌进行攻击时保持健康。接下来，在口服给予10⁹或10¹⁰ SFL114细菌的志愿者中研究了SFL114的安全性和免疫原性。在25名给予10⁹活SFL114细菌的志愿者中有3名（12%），在24名给予10¹⁰活SFL114细菌的志愿者中有13名（54%）报告了持续1 - 2天的轻度肠道不适。记录到对弗氏志贺菌O抗原的局部肠道分泌型IgA反应。体外和体内结果表明，aroD转导菌株SFL114具有口服活候选疫苗所需的特性。