Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2.
Cell Res
; 31(9): 1011-1023, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1315592
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Binding
/
Protein Domains
/
Immunogenicity, Vaccine
/
COVID-19 Vaccines
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Vaccines
/
Variants
Limits:
Adolescent
/
Adult
/
Animals
/
Female
/
Humans
/
Middle aged
/
Young adult
Language:
English
Journal:
Cell Res
Year:
2021
Document Type:
Article
Affiliation country:
S41422-021-00531-8
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