Department of Animal Models and Preclinical Studies, Finlay Institute, Siboney, Playa, Habana, Cuba.
Arch Med Res. 2009 Oct;40(7):527-35. doi: 10.1016/j.arcmed.2009.09.003.
A live attenuated vaccine candidate against human cholera has been developed from the genetically modified Vibrio cholerae O1, biotype El Tor, serotype Ogawa, 638 strain. Previous single dose toxicity and local tolerance studies have demonstrated that the product is innocuous in Sprague Dawley rats by oral route and single dose. The present paper describes a repeated dose toxicity study using a further dose compared to the proposed clinical schedule.
Sprague Dawley rats (140-180g) were treated with two doses of the vaccine candidate with a dedicated placebo formulation or were not treated at all (controls). The test products were inoculated at a 21-day interval. Animals were observed daily, body weight was determined weekly and food and water intakes were measured every other day. Three and 14 days after the last inoculation, groups of rats were humanely sacrificed, bled and macroscopically examined. Blood samples were taken for hematology, serum biochemistry and to determine the vibriocide antibody titers. A comprehensive list of tissue and organ samples was taken for microscopic studies.
There was no mortality and no animal showed any clinical symptoms. Food and water intake, body weight, and hematological and biochemical variables did not show differences of toxicological and/or statistical relevance among the experimental groups. Macroscopic examination did not demonstrate any alterations and there were no histological findings of toxicological significance.
The vaccine was considered potentially safe for human use as indicated by the results in Sprague Dawley rats.
一种针对人类霍乱的减毒活疫苗候选物已从基因改造的霍乱弧菌 O1、生物型 El Tor、血清型 Ogawa、638 株中开发出来。先前的单次毒性和局部耐受性研究表明，该产品通过口服途径和单次剂量对 Sprague Dawley 大鼠是无害的。本文描述了一项使用比拟议临床方案更高剂量的重复剂量毒性研究。
Sprague Dawley 大鼠（140-180g）用两剂疫苗候选物和专门的安慰剂制剂进行处理，或者根本不处理（对照组）。测试产品在 21 天的间隔内接种。每天观察动物，每周测定体重，每隔一天测定食物和水的摄入量。在最后一次接种后 3 天和 14 天，一组大鼠被人道处死，采血并进行大体检查。采集血液样本进行血液学、血清生化检查，并测定杀弧菌抗体滴度。对大量组织和器官样本进行了微观研究。
没有死亡，没有动物出现任何临床症状。实验组之间的食物和水摄入、体重、血液学和生化变量没有表现出毒性和/或统计学上的差异。大体检查未显示任何改变，也没有发现具有毒性意义的组织学发现。
根据 Sprague Dawley 大鼠的结果，该疫苗被认为对人类使用具有潜在安全性。
