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Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for the effectiveness of glycoconjugate vaccine candidates.

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Carboni F, Kitowski A, Sorieul C, Veggi D, Marques MC, Oldrini D, Balducci E, Brogioni B, Del Bino L, Corrado A, Angiolini F, Dello Iacono L, Margarit I, Romano MR, Bernardes GJL, Adamo R
OpenAccess logo Chem Sci 13 2440-2449 (2022)
Cited: 3 times
EuropePMC logo PMID: 35310500

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 the 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 as disulfide bonds, can have a dramatic effect on protein immunogenicity.

Articles - 7o4w mentioned but not cited (2)

  1. Retaining the structural integrity of disulfide bonds in diphtheria toxoid carrier protein is crucial for the effectiveness of glycoconjugate vaccine candidates. Carboni F, Kitowski A, Sorieul C, Veggi D, Marques MC, Oldrini D, Balducci E, Brogioni B, Del Bino L, Corrado A, Angiolini F, Dello Iacono L, Margarit I, Romano MR, Bernardes GJL, Adamo R. Chem Sci 13 2440-2449 (2022)
  2. Monomeric crystal structure of the vaccine carrier protein CRM197 and implications for vaccine development. Gallagher DT, Oganesyan N, Lees A. Acta Crystallogr F Struct Biol Commun 79 82-86 (2023)


Articles citing this publication (1)

  1. Site-Specific Multi-Functionalization of the Carrier Protein CRM197 by Disulfide Rebridging for Conjugate Vaccine Development. Trattnig N, Li Z, Bosman GP, Kosma P, Boons GJ. Chembiochem 23 e202200408 (2022)


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