dc.contributor |
Landspitali - The National University Hospital of Iceland |
dc.contributor.author |
Micoli, Francesca |
dc.contributor.author |
Bjarnarson, Stefania P. |
dc.contributor.author |
Arcuri, Melissa |
dc.contributor.author |
Pind, Audur Anna Aradottir |
dc.contributor.author |
Magnusdottir, Gudbjorg J. |
dc.contributor.author |
Necchi, Francesca |
dc.contributor.author |
Di Benedetto, Roberta |
dc.contributor.author |
Carducci, Martina |
dc.contributor.author |
Schiavo, Fabiola |
dc.contributor.author |
Giannelli, Carlo |
dc.contributor.author |
Pisoni, Ivan |
dc.contributor.author |
Martin, Laura B. |
dc.contributor.author |
Del Giudice, Giuseppe |
dc.contributor.author |
MacLennan, Calman A. |
dc.contributor.author |
Rappuoli, Rino |
dc.contributor.author |
Jonsdottir, Ingileif |
dc.contributor.author |
Saul, Allan |
dc.date.accessioned |
2022-09-10T01:00:59Z |
dc.date.available |
2022-09-10T01:00:59Z |
dc.date.issued |
2020-09-29 |
dc.identifier.citation |
Micoli , F , Bjarnarson , S P , Arcuri , M , Pind , A A A , Magnusdottir , G J , Necchi , F , Di Benedetto , R , Carducci , M , Schiavo , F , Giannelli , C , Pisoni , I , Martin , L B , Del Giudice , G , MacLennan , C A , Rappuoli , R , Jonsdottir , I & Saul , A 2020 , ' Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM 197 conjugate vaccine ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 117 , no. 39 , pp. 24443-24449 . https://doi.org/10.1073/pnas.2005857117 |
dc.identifier.issn |
0027-8424 |
dc.identifier.other |
36967242 |
dc.identifier.other |
f7813d2d-692b-4693-a8d2-6353f806bad6 |
dc.identifier.other |
85092289141 |
dc.identifier.other |
32900928 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/3444 |
dc.description |
Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved. |
dc.description.abstract |
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. |
dc.format.extent |
7 |
dc.format.extent |
1425204 |
dc.format.extent |
24443-24449 |
dc.language.iso |
en |
dc.relation.ispartofseries |
Proceedings of the National Academy of Sciences of the United States of America; 117(39) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Conjugate vaccine |
dc.subject |
Polysaccharide |
dc.subject |
Salmonella Typhi |
dc.subject |
T-dependent response |
dc.subject |
T-independent response |
dc.subject |
Multidisciplinary |
dc.title |
Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine |
dc.type |
/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.1073/pnas.2005857117 |
dc.relation.url |
http://www.scopus.com/inward/record.url?scp=85092289141&partnerID=8YFLogxK |
dc.contributor.department |
Clinical Laboratory Services, Diagnostics and Blood Bank |
dc.contributor.department |
Faculty of Medicine |
dc.contributor.school |
Health Sciences |