Document Type
Article
Publication Date
3-23-2023
Abstract
Because of the rapid mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective vaccine against SARS-CoV-2 variants is needed to prevent coronavirus disease 2019 (COVID-19). T cells, in addition to neutralizing antibodies, are an important component of naturally acquired protective immunity, and a number of studies have shown that T cells induced by natural infection or vaccination contribute significantly to protection against several viral infections including SARS-CoV-2. However, it has never been tested whether a T cell-inducing vaccine can provide significant protection against SARS-CoV-2 infection in the absence of preexisting antibodies. In this study, we designed and evaluated lipid nanoparticle (LNP) formulated mRNA vaccines that induce only T cell responses or both T cell and neutralizing antibody responses by using two mRNAs. One mRNA encodes SARS-CoV-2 Omicron Spike protein in prefusion conformation for induction of neutralizing antibodies. The other mRNA encodes over one hundred T cell epitopes (multi-T cell epitope or MTE) derived from non-Spike but conserved regions of the SARS-CoV-2. We show immunization with MTE mRNA alone protected mice from lethal challenge with the SARS-CoV-2 Delta variant or a mouse-adapted virus MA30. Immunization with both mRNAs induced the best protection with the lowest viral titer in the lung. These results demonstrate that induction of T cell responses, in the absence of preexisting antibodies, is sufficient to confer protection against severe disease, and that a vaccine containing mRNAs encoding both the Spike and MTE could be further developed as a universal SARS-CoV-2 vaccine.
Recommended Citation
Qin, Jane; Jeon, Ju Hyeong; Xu, Jiangsheng; Langston, Laura Katherine; Marasini, Ramesh; Mou, Stephanie; Montoya, Brian; Melo-Silva, Carolina R; Jeon, Hyo Jin; Zhu, Tianyi; Sigal, Luis J.; Xu, Renhuan; and Zhu, Huabin, "Design and Preclinical Evaluation of a Universal SARS-CoV-2 mRNA Vaccine" (2023). Department of Microbiology and Immunology Faculty Papers. Paper 174.
https://jdc.jefferson.edu/mifp/174
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
37033973
Language
English
Comments
This article, which was first published by Frontiers Media, is the author's final published version in Frontiers in Immunology, Volume 14, 2023, Article number 1126392.
The published version is available at https://doi.org/10.3389/fimmu.2023.1126392.
Copyright © 2023 Qin, Jeon, Xu, Langston, Marasini, Mou, Montoya, Melo-Silva, Jeon, Zhu, Sigal, Xu and Zhu
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