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- Title
Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models.
- Authors
Hajnik, Renee L.; Plante, Jessica A.; Liang, Yuejin; Alameh, Mohamad-Gabriel; Tang, Jinyi; Bonam, Srinivasa Reddy; Zhong, Chaojie; Adam, Awadalkareem; Scharton, Dionna; Rafael, Grace H.; Liu, Yang; Hazell, Nicholas C.; Sun, Jiaren; Soong, Lynn; Shi, Pei-Yong; Wang, Tian; Walker, David H.; Sun, Jie; Weissman, Drew; Weaver, Scott C.
- 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. Doubling up on antigens: As additional SARS-CoV-2 variants evolve, vaccines that maintain efficacy across these variants become increasingly important. Here, Hajnik et al. tested whether an mRNA vaccine encoding the more conserved nucleocapsid (N) protein of SARS-CoV-2 can elicit responses that protect against SARS-CoV-2 challenge in vivo. mRNA-N vaccination alone elicited immune responses that could control SARS-CoV-2. Furthermore, combining mRNA-N vaccination with an mRNA vaccine encoding the spike protein (mRNA-S+N) induced better viral control than mRNA-S vaccination alone, including against the Omicron variant. Thus, incorporating the N protein into SARS-CoV-2 vaccines may promote protection against existing and future variants.
- Subjects
SARS-CoV-2 Omicron variant; SARS-CoV-2 Delta variant; VACCINATION; SARS-CoV-2; ANIMAL models in research; MESSENGER RNA; ACTION potentials
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 662, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abq1945