Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models.
Sci Transl Med
; 14(662): eabq1945, 2022 09 14.
Article
in English
| MEDLINE | ID: covidwho-2029465
ABSTRACT
Emergence of SARS-CoV-2 variants of concern (VOCs), including the highly transmissible Omicron and Delta strains, has posed constant challenges to the current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified messenger RNA (mRNA) vaccine that expresses the more conserved viral nucleoprotein (mRNA-N) and show that mRNA-N vaccination alone can induce modest control of SARS-CoV-2. Critically, combining mRNA-N with the clinically proven S-expressing mRNA vaccine (mRNA-S+N) induced robust protection against both Delta and Omicron variants. In the hamster models of SARS-CoV-2 VOC challenge, we demonstrated that, compared to mRNA-S alone, combination mRNA-S+N vaccination not only induced more robust control of the Delta and Omicron variants in the lungs but also provided enhanced protection in the upper respiratory tract. In vivo CD8+ T cell depletion suggested a potential role for CD8+ T cells in protection conferred by mRNA-S+N vaccination. Antigen-specific immune analyses indicated that N-specific immunity, as well as augmented S-specific immunity, was associated with enhanced protection elicited by the combination mRNA vaccination. Our findings suggest that combined mRNA-S+N vaccination is an effective approach for promoting broad protection against SARS-CoV-2 variants.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Vaccines
/
COVID-19
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Transl Med
Journal subject:
Science
/
Medicine
Year:
2022
Document Type:
Article
Affiliation country:
Scitranslmed.abq1945
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