PMID- 21813665 OWN - NLM STAT- MEDLINE DCOM- 20120123 LR - 20211216 IS - 1556-679X (Electronic) IS - 1556-6811 (Print) IS - 1556-679X (Linking) VI - 18 IP - 10 DP - 2011 Oct TI - A tripartite fusion, FaeG-FedF-LT(192)A2:B, of enterotoxigenic Escherichia coli (ETEC) elicits antibodies that neutralize cholera toxin, inhibit adherence of K88 (F4) and F18 fimbriae, and protect pigs against K88ac/heat-labile toxin infection. PG - 1593-9 LID - 10.1128/CVI.05120-11 [doi] AB - Enterotoxigenic Escherichia coli (ETEC) strains expressing K88 (F4) or F18 fimbriae and heat-labile (LT) and/or heat-stable (ST) toxins are the major cause of diarrhea in young pigs. Effective vaccines inducing antiadhesin (anti-K88 and anti-F18) and antitoxin (anti-LT and anti-ST) immunity would provide broad protection to young pigs against ETEC. In this study, we genetically fused nucleotides coding for peptides from K88ac major subunit FaeG, F18 minor subunit FedF, and LT toxoid (LT(192)) A2 and B subunits for a tripartite adhesin-adhesin-toxoid fusion (FaeG-FedF-LT(192)A2:B). This fusion was used for immunizations in mice and pigs to assess the induction of antiadhesin and antitoxin antibodies. In addition, protection by the elicited antiadhesin and antitoxin antibodies against a porcine ETEC strain was evaluated in a gnotobiotic piglet challenge model. The data showed that this FaeG-FedF-LT(192)A2:B fusion elicited anti-K88, anti-F18, and anti-LT antibodies in immunized mice and pigs. In addition, the anti-porcine antibodies elicited neutralized cholera toxin and inhibited adherence against both K88 and F18 fimbriae. Moreover, immunized piglets were protected when challenged with ETEC strain 30302 (K88ac/LT/STb) and did not develop clinical disease. In contrast, all control nonvaccinated piglets developed severe diarrhea and dehydration after being challenged with the same ETEC strain. This study clearly demonstrated that this FaeG-FedF-LT(192)A2:B fusion antigen elicited antibodies that neutralized LT toxin and inhibited the adherence of K88 and F18 fimbrial E. coli strains and that this fusion could serve as an antigen for vaccines against porcine ETEC diarrhea. In addition, the adhesin-toxoid fusion approach used in this study may provide important information for developing effective vaccines against human ETEC diarrhea. FAU - Ruan, Xiaosai AU - Ruan X AD - Vaccinology/Veterinary & Biomedical Sciences Department/The Center for Infectious Disease Research, Box 2157, South Dakota State University, Brookings, SD 57006, USA. FAU - Liu, Mei AU - Liu M FAU - Casey, Thomas A AU - Casey TA FAU - Zhang, Weiping AU - Zhang W LA - eng GR - R21 AI083897/AI/NIAID NIH HHS/United States GR - AI083897/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110803 PL - United States TA - Clin Vaccine Immunol JT - Clinical and vaccine immunology : CVI JID - 101252125 RN - 0 (Adhesins, Bacterial) RN - 0 (Adhesins, Escherichia coli) RN - 0 (Antibodies, Bacterial) RN - 0 (Antigens, Bacterial) RN - 0 (Antitoxins) RN - 0 (Bacterial Toxins) RN - 0 (Enterotoxins) RN - 0 (Escherichia coli Proteins) RN - 0 (Escherichia coli Vaccines) RN - 0 (FaeG protein, E coli) RN - 0 (FedA protein, E coli) RN - 0 (FedF protein, E coli) RN - 0 (K88 antigen, E coli) RN - 0 (Recombinant Fusion Proteins) RN - 147680-16-8 (Fimbriae Proteins) RN - 9012-63-9 (Cholera Toxin) RN - D9K3SN2LNY (heat-labile enterotoxin, E coli) SB - IM MH - Adhesins, Bacterial/genetics/*immunology MH - Adhesins, Escherichia coli/genetics/*immunology MH - Animals MH - Antibodies, Bacterial/blood MH - Antigens, Bacterial MH - Antitoxins/blood MH - Bacterial Toxins/genetics/*immunology MH - Cholera Toxin/antagonists & inhibitors MH - Diarrhea/pathology/prevention & control/veterinary MH - Enterotoxigenic Escherichia coli/genetics/*immunology MH - Enterotoxins/genetics/*immunology MH - Escherichia coli Infections/pathology/prevention & control/*veterinary MH - Escherichia coli Proteins/antagonists & inhibitors/genetics/*immunology MH - Escherichia coli Vaccines/administration & dosage/genetics/*immunology MH - Fimbriae Proteins/antagonists & inhibitors MH - Mice MH - Recombinant Fusion Proteins/genetics/immunology MH - Swine MH - Swine Diseases/pathology/*prevention & control PMC - PMC3187021 EDAT- 2011/08/05 06:00 MHDA- 2012/01/24 06:00 PMCR- 2012/04/01 CRDT- 2011/08/05 06:00 PHST- 2011/08/05 06:00 [entrez] PHST- 2011/08/05 06:00 [pubmed] PHST- 2012/01/24 06:00 [medline] PHST- 2012/04/01 00:00 [pmc-release] AID - CVI.05120-11 [pii] AID - 5120-11 [pii] AID - 10.1128/CVI.05120-11 [doi] PST - ppublish SO - Clin Vaccine Immunol. 2011 Oct;18(10):1593-9. doi: 10.1128/CVI.05120-11. Epub 2011 Aug 3.