Impact Factor 3.782 | CiteScore 3.51
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Chem. | doi: 10.3389/fchem.2019.00726

Site-Specific Conjugation for Fully Controlled Glycoconjugate Vaccine Preparation

 Aline Pillot1, 2, Alain Defontaine1, 2, Amina Fateh1, 2, Annie Lambert1, 2, Maruthi Prasanna1, 2, 3, 4, Mathieu Fanuel5, 6,  Muriel Pipelier2, 7,  Noemi Csaba3, 4, Typhaine Violo1, 2,  Cyrille GRANDJEAN1, 2* and Emilie Camberlein1, 2
  • 1UMR6286 Unité de fonctionnalité et Ingénierie des Protéines (UFIP), France
  • 2Université de Nantes, France
  • 3University of Santiago de Compostela, Spain
  • 4Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CiMUS), Spain
  • 5INRA Centre Angers-Nantes Pays de la Loire, France
  • 6Unité Assemblages Interactions Biopolymères, INRA Centre Angers-Nantes Pays de la Loire, France
  • 7UMR6230 Chimie et Interdisciplinarité Synthèse, Analyse, Modélisation (CEISAM), France

Glycoconjugate vaccines are formed of a carbohydrate antigen covalently linked to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. In addition to the nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry, it has long been assumed that the sites at which the carbohydrate antigen is attached impact both structure and the immune response. These important issues can now be addressed thanks to the development of novel chemoselective ligation reactions as well as that of techniques such as site-selective mutagenesis, glycoengineering or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of Streptococcus pneumoniae has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. As a result we observed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and questions the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.

Keywords: Glycoconjugate vaccine, Cysteine mutagenesis, Chemoselective ligation, Protein conjugation, Pneumococcal vaccine, thio/maleimide ligation

Received: 28 Jul 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Pillot, Defontaine, Fateh, Lambert, Prasanna, Fanuel, Pipelier, Csaba, Violo, GRANDJEAN and Camberlein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Cyrille GRANDJEAN, UMR6286 Unité de fonctionnalité et Ingénierie des Protéines (UFIP), Nantes, 44322, Pays de la Loire, France, Cyrille.Grandjean@univ-nantes.fr