Developing a simple, cost-effective proof-of-concept vaccine candidate against EHEC for cattle

Area of Science:

• Veterinary Immunology
• Microbial Pathogenesis
• Vaccine Development

Background:

• Enterohemorrhagic Escherichia coli (EHEC) causes severe human illness, with cattle as the primary reservoir.
• Shiga toxins (Stx) and type III secretion system (T3SS)-mediated attaching and effacing (A/E) lesions are key virulence factors.
• Preharvest vaccination in cattle is crucial for reducing human EHEC exposure.

Purpose of the Study:

• To engineer and produce a chimeric antigen (EIT) for a scalable, cost-effective EHEC vaccine.
• To evaluate the immunogenicity and functional activity of the EIT-based vaccine in mice and cattle.
• To assess the vaccine's potential for broad reactivity against various EHEC serotypes and related pathogens.

Main Methods:

• Engineered a chimeric antigen EIT (EspA36-192-Intimin653-935-Tir258-361) for periplasmic expression and simple thermal extraction.
• Developed a scalable production process avoiding antibiotics and chemical inducers.
• Immunized mice and cattle with EIT-enriched periplasmic fraction (EIT-PF) and assessed antibody responses and functional activity against EHEC.

Main Results:

• EIT-PF immunization in mice induced strong antibody responses and accelerated clearance of E. coli O157 infection.
• A single EIT-PF dose in cattle elicited antibodies recognizing multiple EHEC serotypes, EPEC, and chimera components.
• Antibodies generated by EIT-PF interfered with T3SS-dependent pedestal formation in vitro.

Conclusions:

• EIT-PF is a broadly reactive, proof-of-concept vaccine candidate for cattle against EHEC.
• The developed production method is scalable and cost-effective.
• Further field studies are necessary to confirm efficacy under real-world conditions.