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The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi

In recent years there have been major efforts to develop glycoconjugate vaccines based on the Vi polysaccharide that will protect against Salmonella enterica Typhi infections, particularly typhoid fever, which remains a major public health concern in low-income countries. The design of glycoconjugat...

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Autores principales: Arcuri, M., Di Benedetto, R., Cunningham, A. F., Saul, A., MacLennan, C. A., Micoli, F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747453/
https://www.ncbi.nlm.nih.gov/pubmed/29287062
http://dx.doi.org/10.1371/journal.pone.0189100
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author Arcuri, M.
Di Benedetto, R.
Cunningham, A. F.
Saul, A.
MacLennan, C. A.
Micoli, F.
author_facet Arcuri, M.
Di Benedetto, R.
Cunningham, A. F.
Saul, A.
MacLennan, C. A.
Micoli, F.
author_sort Arcuri, M.
collection PubMed
description In recent years there have been major efforts to develop glycoconjugate vaccines based on the Vi polysaccharide that will protect against Salmonella enterica Typhi infections, particularly typhoid fever, which remains a major public health concern in low-income countries. The design of glycoconjugate vaccines influences the immune responses they elicit. Here we systematically test the response in mice to Vi glycoconjugates that differ in Vi chain length (full-length and fragmented), carrier protein, conjugation chemistry, saccharide to protein ratio and size. We show that the length of Vi chains, but not the ultimate size of the conjugate, has an impact on the anti-Vi IgG immune response induced. Full-length Vi conjugates, independent of the carrier protein, induce peak IgG responses rapidly after just one immunization, and secondary immunization does not enhance the magnitude of these responses. Fragmented Vi linked to CRM(197) and diphtheria toxoid, but not to tetanus toxoid, gives lower anti-Vi antibody responses after the first immunization than full-length Vi conjugates, but antibody titres are similar to those induced by full-length Vi conjugates following a second dose. The chemistry to conjugate Vi to the carrier protein, the linker used, and the saccharide to protein ratio do not significantly alter the response. We conclude that Vi length and carrier protein are the variables that influence the anti-Vi IgG response to immunization the most, while other parameters are of lesser importance.
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spelling pubmed-57474532018-01-26 The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi Arcuri, M. Di Benedetto, R. Cunningham, A. F. Saul, A. MacLennan, C. A. Micoli, F. PLoS One Research Article In recent years there have been major efforts to develop glycoconjugate vaccines based on the Vi polysaccharide that will protect against Salmonella enterica Typhi infections, particularly typhoid fever, which remains a major public health concern in low-income countries. The design of glycoconjugate vaccines influences the immune responses they elicit. Here we systematically test the response in mice to Vi glycoconjugates that differ in Vi chain length (full-length and fragmented), carrier protein, conjugation chemistry, saccharide to protein ratio and size. We show that the length of Vi chains, but not the ultimate size of the conjugate, has an impact on the anti-Vi IgG immune response induced. Full-length Vi conjugates, independent of the carrier protein, induce peak IgG responses rapidly after just one immunization, and secondary immunization does not enhance the magnitude of these responses. Fragmented Vi linked to CRM(197) and diphtheria toxoid, but not to tetanus toxoid, gives lower anti-Vi antibody responses after the first immunization than full-length Vi conjugates, but antibody titres are similar to those induced by full-length Vi conjugates following a second dose. The chemistry to conjugate Vi to the carrier protein, the linker used, and the saccharide to protein ratio do not significantly alter the response. We conclude that Vi length and carrier protein are the variables that influence the anti-Vi IgG response to immunization the most, while other parameters are of lesser importance. Public Library of Science 2017-12-29 /pmc/articles/PMC5747453/ /pubmed/29287062 http://dx.doi.org/10.1371/journal.pone.0189100 Text en © 2017 Arcuri et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Arcuri, M.
Di Benedetto, R.
Cunningham, A. F.
Saul, A.
MacLennan, C. A.
Micoli, F.
The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title_full The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title_fullStr The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title_full_unstemmed The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title_short The influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against Salmonella Typhi
title_sort influence of conjugation variables on the design and immunogenicity of a glycoconjugate vaccine against salmonella typhi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747453/
https://www.ncbi.nlm.nih.gov/pubmed/29287062
http://dx.doi.org/10.1371/journal.pone.0189100
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