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首页> 外文期刊>Infection and immunity >Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108
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Construction and Evaluation of a Safe, Live, Oral Vibrio cholerae Vaccine Candidate, IEM108

机译：IEM108安全，实时，口服霍乱弧菌疫苗候选者的构建和评估

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IEM101, a Vibrio cholerae O1 El Tor Ogawa strain naturally deficient in CTXΦ, was previously selected as a live cholera vaccine candidate. To make a better and safer vaccine that can induce protective immunity against both the bacteria and cholera toxin (CT), a new vaccine candidate, IEM108, was constructed by introducing a ctxB gene and an El Tor-derived rstR gene into IEM101. The ctxB gene codes for the protective antigen CTB subunit, and the rstR gene mediates phage immunity. The stable expression of the two genes was managed by a chromosome-plasmid lethal balanced system based on the housekeeping gene thyA. Immunization studies indicate that IEM108 generates good immune responses against both the bacteria and CT. After a single-dose intraintestinal vaccination with 109 CFU of IEM108, both anti-CTB immunoglobulin G and vibriocidal antibodies were detected in the immunized-rabbit sera. However, only vibriocidal antibodies are detected in rabbits immunized with IEM101. In addition, IEM108 but not IEM101 conferred full protection against the challenges of four wild-type toxigenic strains of V. cholerae O1 and 4 μg of CT protein in a rabbit model. By introducing the rstR gene, the frequency of conjugative transfer of a recombinant El Tor-derived RS2 suicidal plasmid to IEM108 was decreased 100-fold compared to that for IEM101. This indicated that the El Tor-derived rstR cloned in IEM108 was fully functional and could effectively inhibit the El Tor-derived CTXΦ from infecting IEM108. Our results demonstrate that IEM108 is an efficient and safe live oral cholera vaccine candidate that induces antibacterial and antitoxic immunity and CTXΦ phage immunity.
机译：IEM101是天然缺乏CTXΦ的霍乱弧菌 O1 El Tor Ogawa菌株，以前曾被选作活霍乱疫苗候选者。为了制作出一种更好，更安全的疫苗，该疫苗可以诱导针对细菌和霍乱毒素的保护性免疫，通过引入 ctxB 基因和源自El Tor的方法构建了新的候选疫苗IEM108 rstR 基因进入IEM101。 ctxB 基因编码保护性抗原CTB亚基，而 rstR 基因介导噬菌体免疫。通过看家基因 thyA 的染色体-质粒致死平衡系统控制两个基因的稳定表达。免疫研究表明，IEM108对细菌和CT均产生良好的免疫反应。用IEM108的10 9 CFU进行单剂量肠内疫苗接种后，在免疫的兔血清中同时检测到了抗CTB免疫球蛋白G和杀弧菌抗体。但是，在用IEM101免疫的兔子中仅检测到杀弧菌抗体。另外，IEM108而非IEM101赋予了针对四种野生型 V产毒株的挑战的全面保护。兔模型中的霍乱 O1和4μgCT蛋白。通过引入 rstR 基因，重组的El Tor衍生的RS2自杀质粒向IEM108的共轭转移频率比IEM101降低了100倍。这表明在IEM108中克隆的源自Er Tor的 rstR 具有完整的功能，可以有效抑制源自El Tor的CTXΦ感染IEM108。我们的结果表明，IEM108是一种有效且安全的口服霍乱活疫苗候选物，可诱导抗菌和抗毒性免疫以及CTXΦ噬菌体免疫。

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