Designs and Characterization of Subunit Ebola GP Vaccine Candidates: Implications for Immunogenicity.
Details
Serval ID
serval:BIB_AD44132F37DC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Designs and Characterization of Subunit Ebola GP Vaccine Candidates: Implications for Immunogenicity.
Journal
Frontiers in immunology
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
11
Pages
586595
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
Animals, Antibodies, Neutralizing/immunology, Antibodies, Viral/immunology, CHO Cells, Cricetulus, Ebola Vaccines/immunology, Humans, Mice, Vaccines, Subunit/immunology, Viral Envelope Proteins/immunology, Ebola glycoprotein, Ebola virus, glycoprotein, recombinant vaccine, trimeric protein, vaccine
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2020 16:00
Last modification date
08/08/2024 7:38