|Ruan, Xiaosai -|
|Liu, Mei -|
|Zhang, Weiping -|
Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 26, 2011
Publication Date: N/A
Interpretive Summary: Diarrhea in recently weaned piglets is an important problem for swine producers that results in substantial economic loss. Escherichia coli that adhere in the intestines and produce enterotoxins are responsible for causing diarrhea in piglets. Vaccines that prevent Escherichia coli adherence and neutralize enterotoxin are needed to prevent this disease. We constructed a new experimental three part vaccine consisting of genetically linked parts of a mutant non-toxic enterotoxin and two different proteins needed for adherence. This vaccine caused immune responses in mice and pigs that prevented Escherichia coli adherence, inhibited the activity of the enterotoxin and protected piglets from developing diarrhea after inoculation with a diarrhea-producing Escherichia coli. This work demonstrates the potential for combination vaccines for preventing diarrhea caused by Escherichia coli and will eventually benefit swine producers by reducing economic losses caused by this disease.
Technical Abstract: Enterotoxigenic Escherichia coli (ETEC) strains expressing K88 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 anti-adhesin (anti-K88 & anti-F18) and antitoxin (anti-LT & anti-ST) 5 immunity would provide broad protection to young pigs against ETEC. In this study, we genetically fused peptides from K88ac major subunit FaeG, F18 minor subunit FedF, and LT toxoid (LT192) A2 and B subunit for a tripartite adhesin-adhesin-toxoid fusion (FaeG-FedF-8 LT192A2:B). This fusion was used for immunizations in mice and pigs to assess induction of anti-adhesin and antitoxin antibodies. In addition, elicited anti-adhesin and antitoxin antibodies in protection against a porcine ETEC strain was evaluated in a gnotobiotic challenge model. Data showed that this FaeG-FedF-LT192A2:B fusion elicited anti-K88, anti-F18, and anti-LT antibodies in immunized mice and pigs. In addition, elicited anti-porcine antibodies 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 clinic disease. In contrast, all control non-vaccinated piglets developed severe diarrhea and dehydration after being challenged with the same ETEC strain. This study clearly demonstrated that this FaeG-FedF-LT192A2:B fusion antigen elicited antibodies that neutralized CT toxin and inhibited 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.