Finlay Institute, Center for Research-Production of Vaccines, 27th Ave. No. 19805, La Lisa, Ciudad de la Habana 11600, Cuba.
Vaccine. 2011 Apr 27;29(19):3596-9. doi: 10.1016/j.vaccine.2011.02.074. Epub 2011 Mar 6.
Here we further investigate the pharmacological and toxicological properties of a cholera vaccine based on inactivated whole cells presented in either enteric coated (COA) or uncoated (U/C) tablet formulation from Vibrio cholerae C7258 strain. Tablets were dispersed in 2mL drinking water and administered orally to Sprague Dawley rats distributed in five groups (I COA7, II U/C7 immunized at 0, 7, 69days and III COA14, IV U/C14 immunized at 0, 14, 69days and V control group). Serum vibriocidal antibody response was measured after the administration of two doses with an interval of 7-14days. To further investigate the toxicological aspects a third dose was applied 10 weeks after the initial one. Animals were observed daily and water and food consumption was measured every other day. Periodic blood extractions were performed for hematology, biochemistry, and the titer of serum vibriocidal antibodies was determined. Anatomopathological analysis was performed at days 3 or 14 after the third dose. Results from clinical observations, as well as from water and food consumption and body weigh indicated no toxicity of the vaccine product. Meanwhile, no biological differences were found among different groups in hematological, hemo-chemistry, and anatomopathological studies. Moreover, enteric coated and uncoated tablets against human cholera were found to induce an immune response in rats.
在这里,我们进一步研究了基于灭活全细胞的霍乱疫苗的药理学和毒理学特性,该疫苗来自霍乱弧菌 C7258 株,以肠溶包衣(COA)或未包衣(U/C)片剂的形式呈现。将片剂分散在 2mL 饮用水中,口服给予分布在五个组(I COA7、II U/C7 在 0、7、69 天免疫,III COA14、IV U/C14 在 0、14、69 天免疫和 V 对照组)的 Sprague Dawley 大鼠。在两次给药之间间隔 7-14 天后,测量血清杀菌抗体反应。为了进一步研究毒理学方面,在初次给药后 10 周应用了第三剂。每天观察动物,每隔一天测量水和食物的消耗。定期进行血液提取,用于血液学、生物化学以及血清杀菌抗体滴度的测定。在第三次给药后第 3 天或第 14 天进行解剖病理学分析。临床观察、水和食物消耗以及体重的结果表明疫苗产品无毒。同时,在血液学、血液化学和解剖病理学研究中,不同组之间没有发现生物学差异。此外,针对人类霍乱的肠溶包衣和未包衣片剂被发现能够在大鼠中诱导免疫反应。