α-Hemolysin-Aided Oligomerization of the Spike Protein RBD Resulted in Improved Immunogenicity and Neutralization Against SARS-CoV-2 Variants.
Front Immunol
; 12: 757691, 2021.
Article
in English
| MEDLINE | ID: covidwho-1463478
ABSTRACT
The increase in confirmed COVID-19 cases and SARS-CoV-2 variants calls for the development of safe and broad cross-protective vaccines. The RBD of the spike protein was considered to be a safe and effective candidate antigen. However, the low immunogenicity limited its application in vaccine development. Herein, we designed and obtained an RBD heptamer (mHla-RBD) based on a carrier protein-aided assembly strategy. The molecular weight of mHla-RBD is up to 450 kDa, approximately 10 times higher than that of the RBD monomer. When formulated with alum adjuvant, mHla-RBD immunization significantly increased the immunogenicity of RBD, as indicated by increased titers of RBD-specific antibodies, neutralizing antibodies, Th2 cellular immune response, and pseudovirus neutralization activity, when compared to RBD monomer. Furthermore, we confirmed that RBD-specific antibodies predominantly target conformational epitopes, which was approximately 200 times that targeting linear epitopes. Finally, a pseudovirus neutralization assay revealed that neutralizing antibodies induced by mHla-RBD against different SARS-CoV-2 variants were comparable to those against the wild-type virus and showed broad-spectrum neutralizing activity toward different SARS-CoV-2 variants. Our results demonstrated that mHla-RBD is a promising candidate antigen for development of SARS-CoV-2 vaccines and the mHla could serve as a universal carrier protein for antigen design.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Bacterial Proteins
/
Carrier Proteins
/
Th2 Cells
/
Spike Glycoprotein, Coronavirus
/
COVID-19 Vaccines
/
SARS-CoV-2
/
COVID-19
/
Hemolysin Proteins
Type of study:
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Front Immunol
Year:
2021
Document Type:
Article
Affiliation country:
Fimmu.2021.757691
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