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A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice

Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler’s diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that appreciably decrea...

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Autores principales: Williams, Asher J., Warfel, Katherine F., Desai, Primit, Li, Jie, Lee, Jen-Jie, Wong, Derek A., Nguyen, Phuong M., Qin, Yufan, Sobol, Sarah E., Jewett, Michael C., Chang, Yung-Fu, DeLisa, Matthew P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018396/
https://www.ncbi.nlm.nih.gov/pubmed/36936989
http://dx.doi.org/10.3389/fmolb.2023.1085887
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author Williams, Asher J.
Warfel, Katherine F.
Desai, Primit
Li, Jie
Lee, Jen-Jie
Wong, Derek A.
Nguyen, Phuong M.
Qin, Yufan
Sobol, Sarah E.
Jewett, Michael C.
Chang, Yung-Fu
DeLisa, Matthew P.
author_facet Williams, Asher J.
Warfel, Katherine F.
Desai, Primit
Li, Jie
Lee, Jen-Jie
Wong, Derek A.
Nguyen, Phuong M.
Qin, Yufan
Sobol, Sarah E.
Jewett, Michael C.
Chang, Yung-Fu
DeLisa, Matthew P.
author_sort Williams, Asher J.
collection PubMed
description Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler’s diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that appreciably decreases mortality and morbidity associated with ETEC infection among children under the age of 5 years remains an unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes that leverage glycoengineered strains of non-pathogenic E. coli or their cell-free extracts for producing conjugate vaccine candidates against two of the most prevalent O serogroups of ETEC, O148 and O78. Specifically, we demonstrate site-specific installation of O-antigen polysaccharides (O-PS) corresponding to these serogroups onto licensed carrier proteins using the oligosaccharyltransferase PglB from Campylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses in mice and elicit IgG antibodies that possess bactericidal activity against the cognate pathogens. We also show that one of the prototype conjugates decorated with serogroup O148 O-PS reduces ETEC colonization in mice, providing evidence of vaccine-induced mucosal protection. We anticipate that our bacterial cell-based and cell-free platforms will enable creation of multivalent formulations with the potential for broad ETEC serogroup protection and increased access through low-cost biomanufacturing.
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spelling pubmed-100183962023-03-17 A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice Williams, Asher J. Warfel, Katherine F. Desai, Primit Li, Jie Lee, Jen-Jie Wong, Derek A. Nguyen, Phuong M. Qin, Yufan Sobol, Sarah E. Jewett, Michael C. Chang, Yung-Fu DeLisa, Matthew P. Front Mol Biosci Molecular Biosciences Enterotoxigenic Escherichia coli (ETEC) is the primary etiologic agent of traveler’s diarrhea and a major cause of diarrheal disease and death worldwide, especially in infants and young children. Despite significant efforts over the past several decades, an affordable vaccine that appreciably decreases mortality and morbidity associated with ETEC infection among children under the age of 5 years remains an unmet aspirational goal. Here, we describe robust, cost-effective biosynthetic routes that leverage glycoengineered strains of non-pathogenic E. coli or their cell-free extracts for producing conjugate vaccine candidates against two of the most prevalent O serogroups of ETEC, O148 and O78. Specifically, we demonstrate site-specific installation of O-antigen polysaccharides (O-PS) corresponding to these serogroups onto licensed carrier proteins using the oligosaccharyltransferase PglB from Campylobacter jejuni. The resulting conjugates stimulate strong O-PS-specific humoral responses in mice and elicit IgG antibodies that possess bactericidal activity against the cognate pathogens. We also show that one of the prototype conjugates decorated with serogroup O148 O-PS reduces ETEC colonization in mice, providing evidence of vaccine-induced mucosal protection. We anticipate that our bacterial cell-based and cell-free platforms will enable creation of multivalent formulations with the potential for broad ETEC serogroup protection and increased access through low-cost biomanufacturing. Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10018396/ /pubmed/36936989 http://dx.doi.org/10.3389/fmolb.2023.1085887 Text en Copyright © 2023 Williams, Warfel, Desai, Li, Lee, Wong, Nguyen, Qin, Sobol, Jewett, Chang and DeLisa. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Williams, Asher J.
Warfel, Katherine F.
Desai, Primit
Li, Jie
Lee, Jen-Jie
Wong, Derek A.
Nguyen, Phuong M.
Qin, Yufan
Sobol, Sarah E.
Jewett, Michael C.
Chang, Yung-Fu
DeLisa, Matthew P.
A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title_full A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title_fullStr A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title_full_unstemmed A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title_short A low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic Escherichia coli infections in mice
title_sort low-cost recombinant glycoconjugate vaccine confers immunogenicity and protection against enterotoxigenic escherichia coli infections in mice
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018396/
https://www.ncbi.nlm.nih.gov/pubmed/36936989
http://dx.doi.org/10.3389/fmolb.2023.1085887
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