Document Type

Dissertation - University Access Only

Award Date

2012

Degree Name

Doctor of Philosophy (PhD)

Department / School

Veterinary and Biomedical Sciences

First Advisor

Weiping Zhang

Abstract

Enterotoxigenic Escherichia coli (ETEC) strains remain to be the most common bacterial cause of diarrhea in humans and farm animals. Watery diarrhea in neonatal and post-weaning pigs associated with the ETEC strains cause significant economic losses to the swine industry worldwide due to the weight loss, slow growth and death. The key identified virulence factors of ETEC strains are colonization factors (fimbriae or pili) and enterotoxins. ETEC diarrhea diseases start with ETEC colonization to the small intestine and then secretion of enterotoxins which disrupt fluid homeostasis in the small intestinal epithelial cells that leads to diarrhea. Experimental ETEC vaccines could provide broad protections for young pigs against ETEC by inducing anti-adhesin and anti-toxins immune responses. Porcine ETEC strains that expressing K88 (F4) or Fl8 fimbriae are the common pathogens associated with the post-weaning diarrhea in pigs. Toxins elaborated by porcine ETEC strains include heat-labile (LT), heat-stable (STa and STb ), Shiga toxin 2e (Stx2e), and enteroaggregative heat-stable toxin 1 (EASTl). However, ETEC strains expressing K88 or Fl 8 fimbriae and LT and ST (STa and STb) toxins are the most commonly associated with post-weaning diarrhea. Fimbriae and heat-labile toxin are the key virulence factors, which are also strongly immunogenic. Therefore, it is feasible to develop multivalent vaccines against ETEC by inducing anti-adhesin and anti-toxin immunities. In the studies presented in this dissertation, we genetically constructed an adhesin-toxin chimera containing the receptor-binding domains of K88ac (FaeG), Fl 8 (FedF) and L TA2 and B subunits. Based on the backbone of this chimera, both an experimental subunit vaccine and a modified live vaccine have been developed and tested in mice and pigs. Anti-adhesin and anti-toxin antibodies from immunized mice and pigs were examined. In addition, gnotobiotic piglets challenge studies showed the protection of these two vaccine candidates. Approaches used in this study may provide useful information for developing effective vaccines against human ETEC diarrhea.

Library of Congress Subject Headings

Escherichia coli infections in swine
Vaccines
Enterotoxins

Publisher

South Dakota State University

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Rights Statement

In Copyright