TY - JOUR
T1 - Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models
AU - Hajnik, Renee L.
AU - Plante, Jessica
AU - Liang, Yuejin
AU - Alameh, Mohamad Gabriel
AU - Tang, Jinyi
AU - Bonam, Srinivasa Reddy
AU - Zhong, Chaojie
AU - Adam, Awadalkareem
AU - Scharton, Dionna
AU - Rafael, Grace H.
AU - Liu, Yang
AU - Hazell, Nicholas C.
AU - Sun, Jiaren
AU - Soong, Lynn
AU - Shi, Pei-Yong
AU - Wang, Tian
AU - Walker, David H.
AU - Sun, Jie
AU - Weissman, Drew
AU - Weaver, Scott C.
AU - Plante, Kenneth S.
AU - Hu, Haitao
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/9/14
Y1 - 2022/9/14
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85138449242&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abq1945
DO - 10.1126/scitranslmed.abq1945
M3 - Article
C2 - 36103514
AN - SCOPUS:85138449242
SN - 1946-6234
VL - 14
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 662
M1 - abq1945
ER -