Vaccination of cattle with Escherichia coli O157:H7-derived proteins results in humoral and cellular immune responses but does not confer protection against subsequent challenge
Boland, Kathryn Grace
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Escherichia coli O157:H7 is an enteric pathogen of animals and humans that colonizes the gastrointestinal tract and can result in deadly sequelae. Cattle are most frequently colonized at the recto-anal junction and are asymptomatic carriers and shedders of the bacteria, serving as an important reservoir of human infection. Induction of humoral and cellular immune responses via vaccination is a potentially highly effective means of decreasing cattle colonization and shedding and thereby decreasing human infections. Currently available vaccines are administered subcutaneously or intramuscularly, and immune responses have been evaluated solely by systemic immunoglobulin responses. This study evaluated local and systemic lymphoproliferative responses in addition to immunoglobulin responses following subcutaneous or mucosal (rectal) immunization with E. coli O157:H7 outer membrane protein intimin over three trials and a subsequent four challenge trials were conducted to evaluate systemic lymphoproliferative responses to E. coli O157:H7 proteins following experimental oral or rectal inoculation or subcutaneous vaccination and their relationship to bacterial colonization of cattle following oral or rectal challenge. In all seven trials, significant systemic lymphoproliferative responses (P < 0.05) occurred following immunization in the majority of animals, as well as significant immunoglobulin responses (P < 0.001) in all animals. Surprisingly, local responses in the mesorectal lymph nodes in the animals in the initial three trials were very similar between the subcutaneous and mucosal immunization groups. Moreover, these responses appeared targeted rather than generalized, with minimal or absent responses in the associated prescapular lymph nodes of subcutaneously immunized animals. Following challenge in the final four trials, all animals were successfully colonized. No significant difference was seen in colonization levels between treated (vaccinated) or untreated animals in the two vaccination challenge trials by repeated measures one way analysis of variance (ANOVA). Repeated measures ANOVA was also used to compare colonization levels between animals with lymphoproliferative responses above the mean (high responders) and below the mean (low responders) in all four trials, with no significant differences seen. Overall, animals developed significant humoral and cellular immune responses to E. coli O157:H7 proteins following vaccination or experimental exposure, but these responses did not correlate with protection against colonization following challenge.