Development of a broadly protective protein-based multivalent vaccine against cholera and beyond

Vibrio cholerae continues to be a significant global health concern. Using multiepitope fusion antigen (MEFA) vaccinology platform we developed cholera MEFA which presents antigenic domains from virulence factors of V. cholerae, including toxin coregulated pilus A, cholera toxin (CT), sialidase, hemolysin A, and flagellins B, C, and D along with peptide mimics of lipopolysaccharide (LPS). Cholera MEFA elicited antibodies targeting all the virulence factors except LPS in mice. Additionally, adult rabbits demonstrated a remarkable 2-log (99%) reduction in V. cholerae colonization, and newborn rabbits born to mothers who received cholera MEFA acquired antigen-specific antibodies passively, resulting in protection from bacterial intestinal colonization and diarrhea following the challenge with four different strains of V. cholerae. Moreover, in mice, cholera MEFA elicited high immunogenic titers at a low dose of 5µg. It was further observed that on co-administering cholera MEFA with ETEC MEFA, both vaccine candidates retained their immunogenicity in mice against included virulent antigens. Overall, this study underscores the broad immunogenic and cross-protective nature of the polyvalent cholera protein, suggesting its potential as an antigen for a cross-protective cholera vaccine. The use of the infant rabbit passive protection model represents a crucial advancement in preclinical efficacy assessment and may help overcome hurdles in the development of cholera vaccine. The comparable immunogenicity on co-administration with ETEC MEFA further validates the potential use of cholera MEFA in resource-limited settings.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

VMS - Pathobiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Upadhyay, Ipshita

Contributors dc:contributor

• Zhang, Weiping
• Maddox, Carol
• Lau, Gee
• Steelman, Andrew

• Vaccine
• Cholera
• Pre-clinical
• Mice
• Rabbits
• Mefa
• In-silico
• Computational
• Cholera Mefa
• Vibrio Cholerae

Statement dc:rights

• Copyright 2023 Ipshita Upadhyay

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122129

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122129