Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models
Renee L. Hajnik, Jessica A. Plante, Yuejin Liang, Mohamad‐Gabriel Alameh, Jinyi Tang, Srinivasa Reddy Bonam, Chaojie Zhong, Awadalkareem Adam, Dionna Scharton, Grace Rafael, Yang Liu, Nicholas C. Hazell, Jiaren Sun, Lynn Soong, Pei‐Yong Shi, Tian Wang, David H. Walker, Jie Sun, Drew Weissman, Scott C. Weaver, Kenneth S. Plante, Haitao Hu
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.