Reverse vaccinology and host-pathogen analysis reveal pagP as a promising universal vaccine candidate against avian pathogenic Escherichia coli in poultry

Authors: JIA, L - Mississippi State University; YE, X - Mississippi State University; ARICK II, M - Mississippi State University; HSU, C - Mississippi State University; Evans, Jeffrey; ADHIKARI, P - Mississippi State University; Robinson, Kelsy; ZHANG, L - Mississippi State University

Submitted to: Journal of Applied Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/25/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: Avian Pathogenic Escherichia coli (APEC) is responsible for the systemic disease colibacillosis which poses a serious threat to the health, welfare, and productivity of commercial poultry. Current APEC vaccines lack the ability to protect against the wide variety of strains known to infect commercial poultry creating an urgent need for more effective vaccine candidates. This study used state-of-the-art reverse vaccinology techniques in combination with laboratory techniques to identify antigens that are conserved among multiple APEC strains for novel vaccine development. Evaluation of genomic data from 25 APEC isolated revealed 32 antigenic, highly-conserved proteins with 13 of those being identified as being viable vaccine targets. Host-pathogen interaction studies revealed the pagP protein to be highly upregulated in APEC isolates interacting with host cells indicating it as the most viable candidate for the development of a novel, recombinant subunit vaccine.

Technical Abstract: Avian pathogenic Escherichia coli (APEC) causes colibacillosis, requiring effective vaccines to prevent this devastating disease in poultry. Current strain-specific vaccines show limited protection against diverse APEC strains, highlighting the need to identify conserved antigens for broad-protective vaccine development. This study combines reverse vaccinology analysis of APEC whole genome sequences to identify universal vaccine candidates, with host-pathogen interaction studies to evaluate candidate expression and host immune responses. These complementary approaches aim to identify and select potential antigens for the development of broad-spectrum vaccines against APEC infections in poultry. A total of 3,061 core genome protein coding sequences were predicted from 25 APEC isolates, including 44 proteins that met the criteria of subcellular localization (extracellular and outer membrane), number of transmembrane helix (0 or 1), and adhesion probability score (= 0.5). Among them, 32 proteins were antigenic (antigen score = 0.5) and highly conserved across the E. coli database. Finally, 13 vaccine candidates were predicted to have the immunogenicity potential. During the host-pathogen interaction, selected E. coli isolates induced a host immune reaction (for all P = 0.05), and among the 13 predicted vaccines, pagP showed a highly upregulated expression level during the interaction (P = 0.05). The integration of reverse vaccinology and host-pathogen interaction analysis identified 13 candidate vaccines from APEC strains, with pagP emerging as the main target for the development of recombinant vaccines.