Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for effectiveness of glycoconjugate vaccine candidates
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Authors
carboni, F
kitowski, A
Sorieul, C
Veggi, D
Marques, M
Oldrini, D
Balducci, E
Brogioni, B
Del Bino, L
Corrado, A
Angiolini, F
Dello Iacono, L
Margarit, I
Romano, M
Adamo, R
Journal Title
Chemical Science
ISSN
2041-6520
Publisher
Royal Society of Chemistry
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Lopes Bernardes, G., carboni, F., kitowski, A., Sorieul, C., Veggi, D., Marques, M., Oldrini, D., et al. (2022). Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for effectiveness of glycoconjugate vaccine candidates. Chemical Science https://doi.org/10.1039/D1SC01928G
Abstract
The introduction of glycoconjugate vaccines marks an important point in the fight against various infectious diseases. The covalent conjugation of relevant polysaccharide antigens to immunogenic carrier proteins enables the induction of a long-lasting and robust IgG antibody response, which is not observed for pure polysaccharide vaccines. Although there has been remarkable progress in the development of glycoconjugate vaccines, many crucial parameters remain poorly understood. In particular, the influence of the conjugation site and strategy on immunogenic properties of the final glycoconjugate vaccine is the focus of intense research. Here, we present a comparison of two cysteine selective conjugation strategies, elucidating the impact of both modifications on the structural integrity of the carrier protein, as well as on the immunogenic properties of the resulting glycoconjugate vaccine candidates. Our work suggests that conjugation chemistries impairing structurally relevant elements of the protein carrier, such disulfide bonds, can have a dramatic effect on protein immunogenicity.
Sponsorship
Marie Skłodowska-Curie grant agreement No. 675671. CS is recipient of the the grant No 861194 (PAVax) under EU Horizon 2020 program.
Identifiers
External DOI: https://doi.org/10.1039/D1SC01928G
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333668
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