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Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine
Polysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fraction...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533886/ https://www.ncbi.nlm.nih.gov/pubmed/32900928 http://dx.doi.org/10.1073/pnas.2005857117 |
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author | Micoli, Francesca Bjarnarson, Stefania P. Arcuri, Melissa Aradottir Pind, Audur Anna Magnusdottir, Gudbjorg J. Necchi, Francesca Di Benedetto, Roberta Carducci, Martina Schiavo, Fabiola Giannelli, Carlo Pisoni, Ivan Martin, Laura B. Del Giudice, Giuseppe MacLennan, Calman A. Rappuoli, Rino Jonsdottir, Ingileif Saul, Allan |
author_facet | Micoli, Francesca Bjarnarson, Stefania P. Arcuri, Melissa Aradottir Pind, Audur Anna Magnusdottir, Gudbjorg J. Necchi, Francesca Di Benedetto, Roberta Carducci, Martina Schiavo, Fabiola Giannelli, Carlo Pisoni, Ivan Martin, Laura B. Del Giudice, Giuseppe MacLennan, Calman A. Rappuoli, Rino Jonsdottir, Ingileif Saul, Allan |
author_sort | Micoli, Francesca |
collection | PubMed |
description | Polysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fractions of Vi polysaccharide with average sizes of 9.5, 22.8, 42.7, 82.0, and 165 kDa were compared. Long-chain-conjugated Vi (165 kDa) induced a response in both wild-type and T cell-deficient mice, suggesting that it maintains a T-independent response. In marked contrast, short-chain Vi (9.5 to 42.7 kDa) conjugates induced a response in wild-type mice but not in T cell-deficient mice, suggesting that the response is dependent on T cell help. Mechanistically, this was explained in neonatal mice, in which long-chain, but not short-chain, Vi conjugate induced late apoptosis of Vi-specific B cells in spleen and early depletion of Vi-specific B cells in bone marrow, resulting in hyporesponsiveness and lack of long-term persistence of Vi-specific IgG in serum and IgG(+) antibody-secreting cells in bone marrow. We conclude that while conjugation of long-chain Vi generates T-dependent antigens, the conjugates also retain T-independent properties, leading to detrimental effects on immune responses. The data reported here may explain some inconsistencies observed in clinical trials and help guide the design of effective conjugate vaccines. |
format | Online Article Text |
id | pubmed-7533886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-75338862020-10-13 Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine Micoli, Francesca Bjarnarson, Stefania P. Arcuri, Melissa Aradottir Pind, Audur Anna Magnusdottir, Gudbjorg J. Necchi, Francesca Di Benedetto, Roberta Carducci, Martina Schiavo, Fabiola Giannelli, Carlo Pisoni, Ivan Martin, Laura B. Del Giudice, Giuseppe MacLennan, Calman A. Rappuoli, Rino Jonsdottir, Ingileif Saul, Allan Proc Natl Acad Sci U S A Biological Sciences Polysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fractions of Vi polysaccharide with average sizes of 9.5, 22.8, 42.7, 82.0, and 165 kDa were compared. Long-chain-conjugated Vi (165 kDa) induced a response in both wild-type and T cell-deficient mice, suggesting that it maintains a T-independent response. In marked contrast, short-chain Vi (9.5 to 42.7 kDa) conjugates induced a response in wild-type mice but not in T cell-deficient mice, suggesting that the response is dependent on T cell help. Mechanistically, this was explained in neonatal mice, in which long-chain, but not short-chain, Vi conjugate induced late apoptosis of Vi-specific B cells in spleen and early depletion of Vi-specific B cells in bone marrow, resulting in hyporesponsiveness and lack of long-term persistence of Vi-specific IgG in serum and IgG(+) antibody-secreting cells in bone marrow. We conclude that while conjugation of long-chain Vi generates T-dependent antigens, the conjugates also retain T-independent properties, leading to detrimental effects on immune responses. The data reported here may explain some inconsistencies observed in clinical trials and help guide the design of effective conjugate vaccines. National Academy of Sciences 2020-09-29 2020-09-08 /pmc/articles/PMC7533886/ /pubmed/32900928 http://dx.doi.org/10.1073/pnas.2005857117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Micoli, Francesca Bjarnarson, Stefania P. Arcuri, Melissa Aradottir Pind, Audur Anna Magnusdottir, Gudbjorg J. Necchi, Francesca Di Benedetto, Roberta Carducci, Martina Schiavo, Fabiola Giannelli, Carlo Pisoni, Ivan Martin, Laura B. Del Giudice, Giuseppe MacLennan, Calman A. Rappuoli, Rino Jonsdottir, Ingileif Saul, Allan Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title_full | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title_fullStr | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title_full_unstemmed | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title_short | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM(197) conjugate vaccine |
title_sort | short vi-polysaccharide abrogates t-independent immune response and hyporesponsiveness elicited by long vi-crm(197) conjugate vaccine |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533886/ https://www.ncbi.nlm.nih.gov/pubmed/32900928 http://dx.doi.org/10.1073/pnas.2005857117 |
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