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

Autor: Laurence A. Mulard, Catherine Guerreiro, Philippe J. Sansonetti, Françoise Thouron, Peter Hoogerhout, Michiel Stork, Tae Hee Kim, Armelle Phalipon, Janny Westdijk, Robert M. F. van der Put
Přispěvatelé: Institute for Translational Vaccinology (INTRAVACC), Chimie des Biomolécules - Chemistry of Biomolecules, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Pathogénie microbienne moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), The research leading to these results has received funding from Institut Pasteur, Agence Nationale pour la Recherche (ANR (France), Grant ANR-06-EMPB-013-02, GLYCOVAX), Korea Science and Engineering Foundation (KOSEF, Postdoctoral fellowship to T.H.K.), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (Grant No. ANR-10-LABX-62-IBEID), and the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant Agreement No. 261472-STOPENTERICS., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-06-EMPB-0013,GLYCOVAX-SF2A,Validation d'un vaccin glycoconjugué chimiquement défini(2006), European Project: 261472,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,STOPENTERICS(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Microbiologie et Maladies infectieuses
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Magnetic Resonance Spectroscopy
Biomedical Engineering
Carbohydrates
Pharmaceutical Science
Bioengineering
chemical and pharmacologic phenomena
01 natural sciences
complex mixtures
Microbiology
03 medical and health sciences
chemistry.chemical_compound
Shigella flexneri
Adjuvants
Immunologic
Conjugate vaccine
Dysentery
Bacillary
Pharmacology
Vaccines
Synthetic
Bioconjugation
biology
010405 organic chemistry
Alum
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Immunogenicity
Organic Chemistry
Toxoid
Reproducibility of Results
biology.organism_classification
3. Good health
0104 chemical sciences
030104 developmental biology
chemistry
Biochemistry
Chromatography
Gel
Alum Compounds
Shigella
[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Hapten
Biotechnology
Conjugate
Zdroj: Bioconjugate Chemistry
Bioconjugate Chemistry, American Chemical Society, 2016, 27 (4), pp.883-92. ⟨10.1021/acs.bioconjchem.5b00617⟩
Bioconjugate Chemistry, 2016, 27 (4), pp.883-92. ⟨10.1021/acs.bioconjchem.5b00617⟩
ISSN: 1043-1802
1520-4812
Popis: International audience; 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.
Databáze: OpenAIRE
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