Document details for 'Immunization of cattle with different combinations of H7 flagellin, Tir, Intimin-531 and EspA results in varying levels of protection against colonization with Escherichia coli O157:H7'

Authors McNeilly, T., Mitchell, M.C., Corbishley, A., Nath, M., Simmonds, H., McAteer, S.P., Mahajan, A., Low, J.C., Smith, D.G.E., Huntley, J.F. and Gally, D.L.
Publication details PLoS ONE 10(5), e0128391.
Keywords E. coli O157, vaccination, cattle, Type III secretion, H7 flagellin
Abstract Enterohemorrhagic Escherichia coli (EHEC) are important human pathogens, causing haemorrhagic colitis and haemolytic uraemic syndrome in humans. E. coli O157:H7 is the most common serotype associated with EHEC infections worldwide, although other non-O157 serotypes cause life-threatening infections. Cattle are a main reservoir of EHEC and intervention strategies aimed at limiting EHEC excretion from cattle are predicted to lower the risk of human infection. We have previously shown that immunization of calves with recombinant versions of the type III secretion system (T3SS)-associated proteins EspA, intimin and Tir from EHEC O157:H7 significantly reduced shedding of EHEC O157 from experimentally-colonized calves, and that protection could be augmented by the addition of H7 flagellin to the vaccine formulation. The main aim of the present study was to evaluate the efficacy of simplified formulations of our current subunit vaccine. A secondary aim was to determine if vaccine-induced antibody responses exhibited cross-reactive potential with antigens from other EHEC serotypes. Immunization with EspA, intimin and Tir resulted in a reduction in mean EHEC O157 shedding following challenge, but not the mean proportion of calves colonized. Removal of Tir resulted in more prolonged shedding, whereas replacement of Tir with H7 flagellin resulted in the highest levels of protection, both in terms of reducing both mean EHEC O157 shedding and the proportion of colonized calves, confirming that targeting both T3SS and H7 flagellin is a highly effective approach. Immunization of calves with recombinant EHEC O157 EspA, intimin and Tir resulted in the generation of antibodies capable of cross-reacting with antigens from non-O157 EHEC serotypes, suggesting that immunization with these antigens may provide a degree of cross-protection against other EHEC serotypes. Further studies are now required to test the efficacy of these vaccines in the field, and to formally test the cross-protective potential of the vaccines against other non-O157 EHEC.
Last updated 2016-01-19

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