霍乱疫苗候选株IEM108对CTXPhi感染的抗性。

Resistance of the cholera vaccine candidate IEM108 against CTXPhi infection.

作者信息

Liu Guangwen, Yan Meiying, Liang Weili, Qi Guoming, Liu Yanqing, Gao Shouyi, Kan Biao

机构信息

National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing 102206, PR China.

出版信息

Vaccine. 2006 Mar 10;24(11):1749-55. doi: 10.1016/j.vaccine.2005.09.059. Epub 2005 Oct 21.

DOI:10.1016/j.vaccine.2005.09.059

PMID:16343705

Abstract

The cholera toxin (CT) genes ctxAB are carried on a lysogenic phage of Vibrio cholerae, CTXPhi, which can transfer ctxAB between toxigenic and nontoxigenic strains of bacteria. This transfer may pose a problem when live oral cholera vaccine is given to people in epidemic areas, because the toxin genes can be reacquired by the vaccine strains. To address this problem, we have constructed a live vaccine candidate, IEM108, which carries an El Tor-derived rstR gene. This gene encodes a repressor and can render bacterial resistance to CTXPhi infection. In this study, we evaluated the resistance of IEM108 against CTXPhi infection by using a CTXPhi marked for chloramphenicol (CAF) resistance and an in vivo model. We found that the cloned rstR gene rendered IEM108 immune to infection with the marked CTXPhi. In addition, the infection rate of IEM108 was even lower than that of the native CTXPhi-positive strain. These results suggest that the vaccine candidate IEM108 is resistant to infection by CTXPhi.

摘要

霍乱毒素（CT）基因ctxAB存在于霍乱弧菌的溶原性噬菌体CTXΦ上，该噬菌体可在产毒素和不产毒素的细菌菌株之间转移ctxAB。当在疫区给人们接种口服霍乱活疫苗时，这种转移可能会带来问题，因为疫苗菌株可能会重新获得毒素基因。为了解决这个问题，我们构建了一种候选活疫苗IEM108，它携带一个源自埃尔托生物型的rstR基因。该基因编码一种阻遏蛋白，可使细菌对CTXΦ感染产生抗性。在本研究中，我们通过使用标记有氯霉素（CAF）抗性的CTXΦ和体内模型，评估了IEM108对CTXΦ感染的抗性。我们发现，克隆的rstR基因使IEM108对标记的CTXΦ感染具有免疫力。此外，IEM108的感染率甚至低于天然的CTXΦ阳性菌株。这些结果表明，候选疫苗IEM108对CTXΦ感染具有抗性。