ArticlePLoS pathogens2020
mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
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- Metabolic syndrome enhances SARS-CoV-2 disease severity and reduces mRNA vaccine efficacy in a mouse model.bioRxiv : the preprint server for biology · 2025Article
- mRNA-LNP vaccine-induced CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung.The Journal of experimental medicine · 2024Article
- Post-acute immunological and behavioral sequelae in mice after Omicron infection.bioRxiv : the preprint server for biology · 2023Article
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- The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model.Frontiers in immunology · 2023Article
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- The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.medRxiv : the preprint server for health sciences · 2022Article
- T cell responses to SARS-CoV-2 in humans and animals.Journal of microbiology (Seoul, Korea) · 2022Review
- MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination.Cellular & molecular immunology · 2022Article
- Article
- Cross-protective immunity following coronavirus vaccination and coronavirus infection.The Journal of clinical investigation · 2021Article
- SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses.NPJ vaccines · 2021Article
- Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study.Endocrine · 2021Article
- Allotypic variation in antigen processing controls antigenic peptide generation from SARS-CoV-2 S1 spike glycoprotein.The Journal of biological chemistry · 2021Article
- SARS-CoV-2 acquisition and immune pathogenesis among school-aged learners in four diverse schools.Pediatric research · 2021Article
- SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19.Cell host & microbe · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Critical to the rapid evaluation of vaccines and antivirals against SARS-CoV-2 is the development of tractable animal models to understand the adaptive immune response to the virus. To this end, the use of common laboratory strains of mice is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Importantly, using this system, we functionally identified the CD4+ and CD8+ structural peptide epitopes targeted during SARS-CoV-2 infection in H2b restricted mice and confirmed their existence in an established model of SARS-CoV-2 pathogenesis. We demonstrated that, identical to what has been seen in humans, the antigen-specific CD8+ T cells in mice primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. As the focus of the immune response in mice is highly similar to that of the humans, the identification of functional murine SARS-CoV-2-specific T cell epitopes provided in this study will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2 infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.