Zhang Chengxian, Zhang Weiping
Veterinary and Biomedical Sciences Department, The Center for Infectious Disease Research and Vaccinology, South Dakota State University, Box 2157, North Campus Drive, Brookings, SD 57006, USA.
Clin Vaccine Immunol. 2010 Dec;17(12):1859-67. doi: 10.1128/CVI.00251-10. Epub 2010 Oct 27.
Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and animals. Bacterial adhesins and heat-labile (LT) and heat-stable (ST) enterotoxins are the virulence determinants in ETEC diarrhea. It is believed that vaccines inducing anti-adhesin immunity to inhibit bacterial adherence and anti-toxin immunity to eliminate toxin activity would provide broad-spectrum protection against ETEC. In this study, an ETEC fimbrial adhesin was used as a platform to express LT and STa for adhesin-toxin fusion antigens to induce anti-toxin and anti-adhesin immunity. An epitope from the B subunit of LT toxin (LTP1, (8)LCSEYRNTQIYTIN(21)) and an STa toxoid epitope ((5)CCELCCNPQCAGCY(18)) were embedded in the FaeG major subunit of E. coli K88ac fimbriae. Constructed K88ac-toxin chimeric fimbriae were harvested and used for rabbit immunization. Immunized rabbits developed anti-K88ac, anti-LT, and anti-STa antibodies. Moreover, induced antibodies not only inhibited adherence of K88ac fimbrial E. coli to porcine small intestinal enterocytes but also neutralized cholera toxin and STa toxin. Data from this study demonstrated that K88ac fimbriae expressing LT and STa epitope antigens elicited neutralizing anti-toxin antibodies and anti-adhesin antibodies and suggested that E. coli fimbriae could serve as a platform for the development of broad-spectrum vaccines against ETEC.
产肠毒素大肠杆菌（ETEC）菌株是人和动物腹泻病的主要病因。细菌黏附素以及不耐热（LT）和耐热（ST）肠毒素是ETEC腹泻中的毒力决定因素。据信，诱导抗黏附素免疫以抑制细菌黏附以及抗毒素免疫以消除毒素活性的疫苗将提供针对ETEC的广谱保护。在本研究中，一种ETEC菌毛黏附素被用作表达LT和STa的平台，以制备黏附素-毒素融合抗原，从而诱导抗毒素和抗黏附素免疫。来自LT毒素B亚基的一个表位（LTP1，(8)LCSEYRNTQIYTIN(21)）和一个STa类毒素表位（(5)CCELCCNPQCAGCY(18)）被嵌入大肠杆菌K88ac菌毛的FaeG主要亚基中。收获构建的K88ac-毒素嵌合菌毛并用于兔免疫。免疫的兔产生了抗K88ac、抗LT和抗STa抗体。此外，诱导产生的抗体不仅抑制了K88ac菌毛大肠杆菌对猪小肠肠上皮细胞的黏附，还中和了霍乱毒素和STa毒素。本研究的数据表明，表达LT和STa表位抗原的K88ac菌毛引发了中和抗毒素抗体和抗黏附素抗体，并表明大肠杆菌菌毛可作为开发针对ETEC的广谱疫苗的平台。
