An In Silico-Designed Chimeric Antigen Confers Broad Protection Against Major Diarrheal Pathogens (Shigella, ETEC,...

Area of Science:

• Vaccinology
• Microbiology
• Immunology

Background:

• Diarrheagenic E. coli (DEC) and Shigella species are major causes of mortality in children under five.
• There is a critical need for a broad-spectrum vaccine to combat these prevalent diarrheal pathogens.

Purpose of the Study:

• To design and evaluate a novel chimeric antigen, SEISL, for its potential as a multipathogen vaccine candidate.
• To assess the immunogenicity and protective efficacy of the SEISL antigen in preclinical models.

Main Methods:

• A chimeric antigen (SEISL) was rationally designed, incorporating virulence determinants from EHEC, ETEC, and Shigella.
• The SEISL antigen was expressed, purified, and confirmed using western blot.
• Immunization studies were conducted in rabbit, guinea pig, and mouse models challenged with specific pathogens.

Main Results:

• SEISL immunization elicited robust protective immune responses across all preclinical models.
• In rabbits, SEISL increased serum IgG and reduced fluid accumulation in ETEC challenge models.
• Guinea pigs showed 71.4% protection against Shigella flexneri, and mice exhibited reduced EHEC O157:H7 fecal shedding.

Conclusions:

• The SEISL antigen demonstrates broad protective immunity against ETEC, EHEC, and Shigella in preclinical settings.
• These findings provide proof-of-concept for the continued development of SEISL as a multipathogen vaccine candidate.