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A Synthetic Carbohydrate Conjugate Vaccine Candidate against Shigellosis: Improved Bioconjugation and Impact of Alum on Immunogenicity.

Abstract : Conjugation chemistry is among the most important parameters governing the efficacy of glycoconjugate vaccines. High robustness is required to ensure high yields and batch to batch reproducibility. Herein, we have established a robust bioconjugation protocol based on the thiol-maleimide addition. Major variables were determined and acceptable margins were investigated for a synthetic pentadecasaccharide-tetanus toxoid conjugate, which is a promising vaccine candidate against Shigella flexneri serotype 2a infection. The optimized process is applicable to any thiol-equipped hapten and provides an efficient control of the hapten:carrier ratio. Moreover, comparison of four S. flexneri 2a glycoconjugates only differing by their pentadecasaccharide:tetanus toxoid ratio confirmed preliminary findings indicating that hapten loading is critical for immunogenicity with an optimal ratio here in the range of 17 ± 5. In addition, the powerful influence of alum on the immunogenicity of a Shigella synthetic carbohydrate-based conjugate vaccine candidate is demonstrated for the first time, with a strong anti-S. flexneri 2a antibody response sustained for more than one year.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01350027
Contributor : Anne Lassailly-Bondaz <>
Submitted on : Friday, July 29, 2016 - 2:37:18 PM
Last modification on : Friday, May 15, 2020 - 5:20:02 PM

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Robert M F van der Put, Tae Hee Kim, Catherine Guerreiro, Françoise Thouron, Peter Hoogerhout, et al.. A Synthetic Carbohydrate Conjugate Vaccine Candidate against Shigellosis: Improved Bioconjugation and Impact of Alum on Immunogenicity.. Bioconjugate Chemistry, American Chemical Society, 2016, 27 (4), pp.883-92. ⟨10.1021/acs.bioconjchem.5b00617⟩. ⟨pasteur-01350027⟩

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