tetano
Editor, Senior Moderator
Front Immunol
. 2023 Mar 23;14:1126392.
doi: 10.3389/fimmu.2023.1126392. eCollection 2023.
Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine
Jane Qin[SUP] 1 [/SUP], Ju Hyeong Jeon[SUP] 1 [/SUP], Jiangsheng Xu[SUP] 1 [/SUP], Laura Katherine Langston[SUP] 1 [/SUP], Ramesh Marasini[SUP] 1 [/SUP], Stephanie Mou[SUP] 1 [/SUP], Brian Montoya[SUP] 2 [/SUP], Carolina R Melo-Silva[SUP] 2 [/SUP], Hyo Jin Jeon[SUP] 1 3 [/SUP], Tianyi Zhu[SUP] 1 4 [/SUP], Luis J Sigal[SUP] 2 [/SUP], Renhuan Xu[SUP] 1 [/SUP], Huabin Zhu[SUP] 1 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; T cell response; mRNA vaccine; multiple T cell epitopes (MTEs); neutralizing antibody.
. 2023 Mar 23;14:1126392.
doi: 10.3389/fimmu.2023.1126392. eCollection 2023.
Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine
Jane Qin[SUP] 1 [/SUP], Ju Hyeong Jeon[SUP] 1 [/SUP], Jiangsheng Xu[SUP] 1 [/SUP], Laura Katherine Langston[SUP] 1 [/SUP], Ramesh Marasini[SUP] 1 [/SUP], Stephanie Mou[SUP] 1 [/SUP], Brian Montoya[SUP] 2 [/SUP], Carolina R Melo-Silva[SUP] 2 [/SUP], Hyo Jin Jeon[SUP] 1 3 [/SUP], Tianyi Zhu[SUP] 1 4 [/SUP], Luis J Sigal[SUP] 2 [/SUP], Renhuan Xu[SUP] 1 [/SUP], Huabin Zhu[SUP] 1 [/SUP]
Affiliations
- PMID: 37033973
- PMCID: PMC10076570
- DOI: 10.3389/fimmu.2023.1126392
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.
Keywords: SARS-CoV-2; T cell response; mRNA vaccine; multiple T cell epitopes (MTEs); neutralizing antibody.