Designs and Characterization of Subunit Ebola GP Vaccine Candidates: Implications for Immunogenicity.
- Agnolon V Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Kiseljak D ExcellGene SA, Monthey, Switzerland.
- Wurm MJ ExcellGene SA, Monthey, Switzerland.
- Wurm FM ExcellGene SA, Monthey, Switzerland.
- Foissard C Université Paris Saclay, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), Département Médicaments et Technologies pour la Santé (DMTS), SPI, Bagnols-sur-Cèze, France.
- Gallais F Université Paris Saclay, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), Département Médicaments et Technologies pour la Santé (DMTS), SPI, Bagnols-sur-Cèze, France.
- Wehrle S Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale De Lausanne (EPFL), Lausanne, Switzerland.
- Muñoz-Fontela C Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
- Bellanger L Université Paris Saclay, Commissariat à l'Energie Atomique et aux énergies alternatives (CEA), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement (INRAE), Département Médicaments et Technologies pour la Santé (DMTS), SPI, Bagnols-sur-Cèze, France.
- Correia BE Laboratory of Protein Design and Immunoengineering, École Polytechnique Fédérale De Lausanne (EPFL), Lausanne, Switzerland.
- Corradin G Department of Biochemistry, Université de Lausanne (UNIL), Epalinges, Switzerland.
- Spertini F Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- 2020-11-30
Published in:
- Frontiers in immunology. - 2020
English
The humoral responses of Ebola virus (EBOV) survivors mainly target the surface glycoprotein GP, and anti-GP neutralizing antibodies have been associated with protection against EBOV infection. In order to elicit protective neutralizing antibodies through vaccination a native-like conformation of the antigen is required. We therefore engineered and expressed in CHO cells several GP variants from EBOV (species Zaire ebolavirus, Mayinga variant), including a soluble GP ΔTM, a mucin-like domain-deleted GP ΔTM-ΔMUC, as well as two GP ΔTM-ΔMUC variants with C-terminal trimerization motifs in order to favor their native trimeric conformation. Inclusion of the trimerization motifs resulted in proteins mimicking GP metastable trimer and showing increased stability. The mucin-like domain appeared not to be critical for the retention of the native conformation of the GP protein, and its removal unmasked several neutralizing epitopes, especially in the trimers. The soluble GP variants inhibited mAbs neutralizing activity in a pseudotype transduction assay, further confirming the proteins' structural integrity. Interestingly, the trimeric GPs, a native-like GP complex, showed stronger affinity for antibodies raised by natural infection in EBOV disease survivors rather than for antibodies raised in volunteers that received the ChAd3-EBOZ vaccine. These results support our hypothesis that neutralizing antibodies are preferentially induced when using a native-like conformation of the GP antigen. The soluble trimeric recombinant GP proteins we developed represent a novel and promising strategy to develop prophylactic vaccines against EBOV and other filoviruses.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.3389/fimmu.2020.586595
- PMID 33250896
- Persistent URL
- https://sonar.ch/global/documents/1083
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