Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits
Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits
复制标题
DOI：
10.1016/s0264-410x(03)00388-8
复制
发表时间：
2003-09-08
期刊：
影响因子：
5.5
通讯作者：
Lubitz, W
中科院分区：
文献类型：
--
作者：
Eko, FO;Schukovskaya, T;Lubitz, W
需要一种有效的霍乱弧菌疫苗来降低这种病原体引起的发病率和死亡率。尽管目前口服疫苗具有可测量的效力，但仍需要在目标人群中开发更有效的广谱效力疫苗。近年来的研究表明，通过克隆裂解基因E的表达产生的细菌幽灵具有佐剂特性和免疫原性。本研究用霍乱弧菌O1或O139制备鬼菌，并在可逆肠结型成年兔腹泻（RITARD）模型中作为疫苗进行评价。用不同剂量的霍乱弧菌鬼影制剂口服免疫家兔。疫苗制剂对指示菌株产生高水平的血清杀弧菌滴度。反应的大小是通过所有家兔的几何平均滴度（GMT）相对于预防接种滴度的增加来测量的。vcg免疫兔血清介导同源和异源菌株的补体依赖性杀伤能力证明了交叉保护的诱导作用。初次免疫后30天，免疫兔可免受十二指肠内攻击。对攻击的保护性免疫似乎是剂量依赖性的，并与定植的显著抑制有关。这些结果表明，vcg代表了霍乱疫苗开发的新途径，是一种有效的疫苗递送载体。2003爱思唯尔科学有限公司版权所有。
An effective Vibrio cholerae vaccine is needed to reduce the morbidity and mortality caused by this pathogen. Despite the availability of current oral vaccines with measurable efficacy, there is need for more effective vaccines with broad-spectrum efficacy in target populations. Recent studies have shown that bacterial ghosts, produced by the expression of cloned lysis gene E, possess adjuvant properties and are immunogenic. In this study, ghosts were prepared from V. choleroe O1 or O139 and evaluated as vaccines in the reversible intestinal tie adult rabbit diarrhea (RITARD) model. Rabbits were orally immunized with different doses of V. cholerae ghost (VCG) formulations. The vaccine formulations elicited high levels of serum vibriocidal titers against indicator strains. The magnitude of the response was measured as the geometric mean titer (GMT) increase for all rabbits in relation to prevaccination titers. The induction of cross protection was evidenced by the ability of serum from VCG-immunized rabbits to mediate complement-dependent killing of both the homologous and the heterologous strains. Immunized rabbits were protected against intraduodenal challenge 30 days after primary immunization. Protective immunity against challenge appeared to be dose dependent and was associated with marked inhibition of colonization. These results indicate that VCGs represent a novel approach to cholera vaccine development and constitute an effective vaccine delivery vehicle. (C) 2003 Elsevier Science Ltd. All rights reserved.