Salmonella Vaccines for Scours

NON-TECHNICAL SUMMARY: Newborn calves are susceptible to scours. There is a need to provide an efficacious vaccine to prevent this disease. The proposed studies are designed to optimize mucosal and systemic antibody responses in heifers to provide passive immunity to newborn calves.

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APPROACH: The focus of our studies is to assess the feasibility of attenuated Salmonella vectors as a vaccine delivery vehicle for cows similar to that described for humans and for chickens. We propose to use attenuated Salmonella vectors as a means of immunizing heifers against bovine enterotoxigenic Escherichia coli (ETEC). We hypothesize that protective immunity to ETEC is dependent upon how the fimbriae is expressed, i.e., extracellular versus intracellular expression. Extracellular expression of fimbrial antigens results in the early induction of IL-4 followed by a concomitant induction of IFN-g. Consequently, elevated fimbriae-specific S-IgA titers are obtained when compared to secretory (S)-IgA levels induced by cytoplasmic expressed Ags. We hypothesize that there are at least two pathways favoring S-IgA generation: the "classical pathway" mediated by the IgA switch factor, TGF-b, in combination with Th2 cytokines, IL-4, IL-5, and IL-6, versus the "alternate pathway" where, in the presence of IFN-g, IL-6 and possibly IL-18-induced IL-13 favor S-IgA production. Thus, it is possible that mode of antigen presentation may drive host immunity either pathway. The goal of these studies is to learn how modifying vaccine formulations to mimic how antigens are naturally or unnaturally presented and these consequences upon host protective responses.
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PROGRESS: 2002/10 TO 2006/09<BR>
OUTPUTS: The focus of our studies is to assess the feasibility of attenuated Salmonella vectors as a vaccine delivery vehicle for cows similar to that described for humans and for chickens. We propose to use attenuated Salmonella vectors as a means of immunizing heifers against bovine enterotoxigenic Escherichia coli (ETEC). We hypothesize that protective immunity to ETEC is dependent upon how the fimbriae is expressed, i.e., extracellular versus intracellular expression. Current studies are examining humoral immunity induced following oral immunization with the bovine ETEC vaccines in heifers for subsequent challenge studies in newborn calves. During this study, we were able to conduct a vaccine trial. Nine heifers were divided into three groups: vector only (three orally immunized with H647), PBS (two given vehicle only), and Salmonella-K99 (four orally immunized with strain AP112). Heifers were given three oral doses of vaccine on days 0, 30, and 60. Thirty days after the last dose, heifers were artificially inseminated. Nine of nine became pregnant, and successfully calved. Newborn calves were allowed to receive colostrum for the first 12 hrs post-parturition, and then challenged with wild-type K99+ ETEC (strain B41). Calves were followed daily and in some instances, supportive fluids were provided. One of two calves from vehicle-treated heifers scoured. This one scouring calf was able to clear after one day the K99+ ETEC, but did later develop a rotavirus infection. Evaluation of fecal CFU revealed that those calves from PBS-treated and H647-vaccinated heifers shed K99+ ETEC for greater lengths of time whereas calves from AP112-vaccinated heifers shed K99+ ETEC for a shorter duration. Thus, these studies suggest that Salmonella-K99 vaccine was effective for stimulating long-lasting immunity in heifers to confer protection for their newborn calves. <BR> PARTICIPANTS: David W. Pascual: PI Xinghong Yang: Investigator Nancy Walters: Investigator Miguel Ascon: post-doc Javier Ochoa-Reparaz: post-doc Theresa Trunkle: Research Associate <BR> <BR>

IMPACT: 2002/10 TO 2006/09<BR>
Currently, the industry lacks an efficacious method for delivering vaccines orally into cattle. Current studies are evaluating the efficiency of Salmonella vectors and other methods as a means to vaccinate cattle against enteric diseases. A successful outcome from these studies will facilitate development of new livestock vaccines.