Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 14, Issue 662, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.abq1945
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Funding
- UTMB Institute for Human Infections and Immunity COVID-19
- Sealy and Smith Foundation
- NIH [AI127744, AI140569, R24AI120942, AI157852, AI147903, AI132674, AI56536, HHSN272201600013C, AI134907, AI145617, UL1TR001439, AI147394, AI112844, AI154598]
- Sealy & Smith Foundation
- Kleberg Foundation
- John S. Dunn Foundation
- Amon G. Carter Foundation
- Gilson Longenbaugh Foundation
- Summerfield Robert Foundation
- UTMB Sealy Institute for Vaccine Sciences Fellowship
- McLaughlin Fellowship
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This study reports a nucleoside-modified mRNA vaccine expressing the viral nucleoprotein, which shows modest control of SARS-CoV-2 when administered alone. However, combining this vaccine with a clinically proven mRNA vaccine expressing the spike protein induces robust protection against both Delta and Omicron variants.
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.
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