2026-09-19T21:40:31Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/122129 2024-03-02 col_2142_5131 col_2142_25441 com_2142_5130 com_2142_25440 com_2142_14833

Zhang, Weiping Zhang, Weiping Maddox, Carol Lau, Gee Steelman, Andrew 2023-12 application/pdf en text Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2025-12-01 The student, Ipshita Upadhyay, accepted the attached license on 2023-11-20 at 15:52. The student, Ipshita Upadhyay, submitted this Dissertation for approval on 2023-11-20 at 16:13. This Dissertation was approved for publication on 2023-11-30 at 13:12. DSpace SAF Submission Ingestion Package generated from Vireo submission #19979 on 2024-03-01 at 13:30:41 Development of a broadly protective protein-based multivalent vaccine against cholera and beyond Upadhyay, Ipshita Vaccine Cholera Pre-clinical Mice Rabbits Mefa In-silico Computational Cholera Mefa Vibrio Cholerae 2023-11-30 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. Text eng https://hdl.handle.net/2142/122129 Copyright 2023 Ipshita Upadhyay Ph.D. Dissertation VMS - Pathobiology University of Illinois at Urbana-Champaign Pathobiology