Ranallo Ryan T, Thakkar Sejal, Chen Qing, Venkatesan Malabi M
Division of Bacterial and Rickettsial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vaccine. 2007 Mar 8;25(12):2269-78. doi: 10.1016/j.vaccine.2006.11.067. Epub 2006 Dec 20.
Recent clinical trials involving live attenuated Shigella vaccine strains SC602 and WRSS1 have revealed that deletion of the virG(icsA) gene dramatically reduces virulence in human volunteers. These strains can be given at low oral doses and induce a strong, and in some cases, protective immune responses. However, residual vaccine associated reactogenicity suggests that further attenuation is required. A recent clinical trial indicated that the set and sen enterotoxin genes contribute to the symptoms of fever and diarrhea observed with live Shigella vaccine strains. Based on these findings, a Shigella flexneri 2a vaccine candidate, WRSf2G11, with deletions in the virG(icsA), set and sen genes has been constructed using the lambda red recombinase system. The immunogenicity and protective efficacy of WRSf2G11 compares favorably with SC602 following either intranasal (IN) or ocular (OC) immunization of guinea pigs. Taken together, these data indicate that second generation virG-based Shigella vaccine strains which lack enterotoxin genes, such as WRSf2G11, will likely show lower levels of reactogenicity without hampering the robust immune responses achieved with previous live vaccines.
近期涉及减毒活志贺氏菌疫苗株SC602和WRSS1的临床试验表明，virG(icsA)基因的缺失显著降低了对人类志愿者的毒力。这些菌株可以低口服剂量给药，并诱导强烈的免疫反应，在某些情况下还具有保护性。然而，疫苗相关的残余反应原性表明需要进一步减毒。最近的一项临床试验表明，志贺氏菌属肠毒素基因与减毒活志贺氏菌疫苗株所观察到的发热和腹泻症状有关。基于这些发现，利用λ红重组酶系统构建了一种弗氏志贺氏菌2a候选疫苗WRSf2G11，该疫苗的virG(icsA)、set和sen基因均有缺失。豚鼠经鼻内（IN）或眼内（OC）免疫后，WRSf2G11的免疫原性和保护效果与SC602相比具有优势。综上所述，这些数据表明，第二代基于virG的缺乏肠毒素基因的志贺氏菌疫苗株，如WRSf2G11，可能会表现出较低水平的反应原性，同时又不会妨碍之前的活疫苗所产生的强大免疫反应。
