Subunit vaccines based on intimin and Efa-1 polypeptides induce humoral immunity in cattle but do not protect against intestinal colonisation by enterohaemorrhagic Escherichia coli O157:H7 or O26:H-

G. Frankel,F. Dziva,A. Abu-Median,T.S. Wallis,P.M. van Diemen,N. Chanter,M.P. Stevens,G. Dougan,H. van den Bosch

doi:10.1016/j.vetimm.2006.12.009

Abstract

Enterohaemorrhagic Escherichia coli (EHEC) infections in humans are an important public health concern and are commonly acquired via contact with ruminant faeces. Cattle are a key control point however cross-protective vaccines for the control of EHEC in the bovine reservoir do not yet exist. The EHEC serogroups that are predominantly associated with human infection in Europe and North America are O157 and O26. Intimin and EHEC factor for adherence (Efa-1) play important roles in intestinal colonisation of cattle by EHEC and are thus attractive candidates for the development of subunit vaccines. Immunisation of calves with the cell-binding domain of intimin subtypes β or γ via the intramuscular route induced antigen-specific serum IgG1 and, in some cases salivary IgA responses, but did not reduce the magnitude or duration of faecal excretion of EHEC O26:H- (Int280-β) or EHEC O157:H7 (Int280-γ) upon subsequent experimental challenge. Similarly, immunisation of calves via the intramuscular route with the truncated Efa-1 protein (Efa-1′) from EHEC O157:H7 or a mixture of the amino-terminal and central thirds of the full-length protein (Efa-1-N and M) did not protect against intestinal colonisation by EHEC O157:H7 (Efa-1′) or EHEC O26:H- (Efa-1-N and M) despite the induction of humoral immunity. A portion of the serum IgG1 elicited by the truncated recombinant antigens in calves was confirmed to recognise native protein exposed on the bacterial surface. Calves immunised with a mixture of Int280-γ and Efa-1′ or an EHEC O157:H7 bacterin via the intramuscular route then boosted via the intranasal route with the same antigens using cholera toxin B subunit as an adjuvant were also not protected against intestinal colonisation by EHEC O157:H7. These studies highlight the need for further studies to develop and test novel vaccines or treatments for control of this important foodborne pathogen.

Highlights

Enterohaemorrhagic Escherichia coli (EHEC) are zoonotic enteric pathogens of worldwide importance
In Europe and North America EHEC infections are predominantly attributed to serotype O157:H7, but infections with non-O157 EHEC are an emerging problem and may be more common than those caused by O157 in some countries (Bettelheim, 2003)
Stochastic simulation models predict that cattle are a key control point to reduce the incidence of EHEC infection in humans (Jordan et al, 1999), until recently the host and bacterial factors influencing intestinal colonisation of cattle by EHEC were poorly understood

Summary

Introduction

Enterohaemorrhagic Escherichia coli (EHEC) are zoonotic enteric pathogens of worldwide importance. Infections in humans may involve acute gastroenteritis and be complicated by haemorrhagic colitis and severe renal and neurological sequelae associated with the production of one or more Shiga toxins. Ruminants are an important reservoir of EHEC (Gansheroff and O’Brien, 2000), and human infections are frequently associated with direct contact with ruminants or their environment (Locking et al, 2001; O’Brien et al, 2001). Consumption of meat, raw milk, vegetables, fruit or water contaminated with ruminant faeces is a risk factor in sporadic cases of human EHEC infection (Caprioli and Tozzi, 1998). Stochastic simulation models predict that cattle are a key control point to reduce the incidence of EHEC infection in humans (Jordan et al, 1999), until recently the host and bacterial factors influencing intestinal colonisation of cattle by EHEC were poorly understood

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