Escherichia coli K88ac fimbriae expressing heat-labile and heat-stable (STa) toxin epitopes elicit antibodies that neutralize cholera toxin and STa toxin and inhibit adherence of K88ac fimbrial E. coli.
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.
Zhang
Chengxian
C
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.
Zhang
Weiping
W
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001422:Bacterial Adhesion / Q000276:immunology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000037:antagonists & inhibitors* / Q000276:immunology; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000382:microbiology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D004927:Escherichia coli Infections / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology*; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D013552:Swine; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D000939:Epitopes; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C026888:K88 antigen, E coli; D014614:Vaccines, Synthetic; C034151:heat stable toxin (E coli); D036781:Fimbriae Proteins; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli