Opin vísindi

Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine

Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine


Title: Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine
Author: Micoli, Francesca
Bjarnarson, Stefania P.
Arcuri, Melissa
Pind, Audur Anna Aradottir
Magnusdottir, Gudbjorg J.
Necchi, Francesca
Di Benedetto, Roberta
Carducci, Martina
Schiavo, Fabiola
Giannelli, Carlo
... 7 more authors Show all authors
Date: 2020-09-29
Language: English
Scope: 7
University/Institute: Landspitali - The National University Hospital of Iceland
School: Health Sciences
Department: Clinical Laboratory Services, Diagnostics and Blood Bank
Faculty of Medicine
Series: Proceedings of the National Academy of Sciences of the United States of America; 117(39)
ISSN: 0027-8424
DOI: https://doi.org/10.1073/pnas.2005857117
Subject: Conjugate vaccine; Polysaccharide; Salmonella Typhi; T-dependent response; T-independent response; Multidisciplinary
URI: https://hdl.handle.net/20.500.11815/3444

Show full item record

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

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.

Description:

Publisher Copyright: © 2020 National Academy of Sciences. All rights reserved.

Files in this item

This item appears in the following Collection(s)