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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, Filippo 
Veggi, Daniele 
Marques, Marta C 


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.



34 Chemical Sciences, Immunization, Prevention, Infectious Diseases, Vaccine Related, Biotechnology, Emerging Infectious Diseases, 1 Underpinning research, 3.4 Vaccines, 3 Prevention of disease and conditions, and promotion of well-being, 1.1 Normal biological development and functioning, 3 Good Health and Well Being

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Chem Sci

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Royal Society of Chemistry (RSC)
Horizon 2020 Framework Programme (675671)