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© Valérie Choumet
Mosquitoes were orally infected with the chikungunya virus. Midguts were dissected at day 5 post-infection, fixed and permeabilised. Virus is shown in red (anti-E2 protein, cyanine 3), the actin network in green (phalloidin 548) and nuclei in blue (DAPI).
Publication : Bioconjugate chemistry

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Bioconjugate chemistry - 21 Mar 2016

van der Put RM, Kim TH, Guerreiro C, Thouron F, Hoogerhout P, Sansonetti PJ, Westdijk J, Stork M, Phalipon A, Mulard LA

Link to Pubmed [PMID] – 26918643

Bioconjug. Chem. 2016 Mar;

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.

http://www.ncbi.nlm.nih.gov/pubmed/26918643