Year: 2021
Type: preprint
Abstract: Emergence of SARS-CoV-2 variants of concern (VOC), including the highly transmissible delta strain, has posed challenges to current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified mRNA vaccine that expresses the more conserved viral nucleoprotein (mRNA-N). We show that mRNA-N alone was able to induce a modest but significant control of SARS-CoV-2 in mice and hamsters. Critically, by combining mRNA-N with the clinically approved S-expressing mRNA vaccine (mRNA-S-2P), we found that combinatorial mRNA vaccination (mRNA-S+N) led to markedly enhanced protection against the SARS-CoV-2 delta variant compared to mRNA-S. In a hamster model, we demonstrated that while mRNA-S alone elicited significant control of the delta strain in the lungs (∼45-fold reduction in viral loads compared to un-vaccinated control), its effectiveness in the upper respiratory tract was weak, whereas combinatorial mRNA-S+N vaccination induced markedly more robust control of the delta variant infection in the lungs (∼450-fold reduction) as well as in the upper respiratory tract (∼20-fold reduction). Immune analyses indicated that induction of N-specific immunity as well as augmented S-specific T-cell response and neutralizing antibody activity were collectively associated the enhanced protection against SARS-CoV-2 delta strain by combinatorial mRNA vaccination. These findings suggest that the combined effects of protection in the lungs and upper respiratory tract could both reduce the risk of severe disease as well as of infection and transmission.
Authors: Renee L. Hajnik, Jessica A. Plante, Yuejin Liang, Mohamad-Gabriel Alameh, Jinyi Tang, Chaojie Zhong, Awadalkareem Adam, Dionna Scharton, Grace H. Rafael, Yang Liu, Nicholas C. Hazell, Jiaren Sun, Lynn Soong, Pei-Yong Shi, Tian Wang, Jie Sun, Drew Weissman, Scott C. Weaver, Kenneth S. Plante, Haitao Hu
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: World Reference Center for Emerging Viruses and Arboviruses (WRCEVA), Regulation of Ebola virus replication by the host ubiquitin system, G2701190842, In vitro and in vivo analysis of susceptibility of Ad26 vector-induced CD4 T cells to HIV/SIV, G5132291675, G5546329050, Pellino-1, a novel target for treatment of congenital Zika syndrome, G7262964771, Revolutionary Eilat-based Chikungunya Vaccine Vector, G9000162387, Modulation of BRD4 to epigenetically suppress HIV, UTMB Clinical and Translational Science Award
OpenAlex ID: W4200419618