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A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections
The arthritogenic alphavirus, chikungunya virus (CHIKV), is now present in almost 100 countries worldwide. Further spread is very likely, which raises public health concerns. CHIKV infections cause fever and arthralgia, which can be debilitating and last for years. Here, we describe a CHIKV vaccine...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126847/ https://www.ncbi.nlm.nih.gov/pubmed/35664702 http://dx.doi.org/10.1016/j.omtn.2022.04.036 |
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author | Schmidt, Christin Haefner, Erik Gerbeth, Julia Beissert, Tim Sahin, Ugur Perkovic, Mario Schnierle, Barbara S. |
author_facet | Schmidt, Christin Haefner, Erik Gerbeth, Julia Beissert, Tim Sahin, Ugur Perkovic, Mario Schnierle, Barbara S. |
author_sort | Schmidt, Christin |
collection | PubMed |
description | The arthritogenic alphavirus, chikungunya virus (CHIKV), is now present in almost 100 countries worldwide. Further spread is very likely, which raises public health concerns. CHIKV infections cause fever and arthralgia, which can be debilitating and last for years. Here, we describe a CHIKV vaccine candidate based on trans-amplifying RNA (taRNA). The vaccine candidate consists of two RNAs: a non-replicating mRNA encoding for the CHIKV nonstructural proteins, forming the replicase complex and a trans-replicon (TR) RNA encoding the CHIKV envelope proteins. The TR-RNA can be amplified by the replicase in trans, and small RNA amounts can induce a potent immune response. The TR-RNA was efficiently amplified by the CHIKV replicase in vitro, leading to high protein expression, comparable to that generated by a CHIKV infection. In addition, the taRNA system did not recombine to replication-competent CHIKV. Using a prime-boost schedule, the vaccine candidate induced potent CHIKV-specific humoral and cellular immune responses in vivo in a mouse model. Notably, mice were protected against a high-dose CHIKV challenge infection with two vaccine doses of only 1.5 μg RNA. Therefore, taRNAs are a promising safe and efficient vaccination strategy against CHIKV infections. |
format | Online Article Text |
id | pubmed-9126847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-91268472022-06-04 A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections Schmidt, Christin Haefner, Erik Gerbeth, Julia Beissert, Tim Sahin, Ugur Perkovic, Mario Schnierle, Barbara S. Mol Ther Nucleic Acids Original Article The arthritogenic alphavirus, chikungunya virus (CHIKV), is now present in almost 100 countries worldwide. Further spread is very likely, which raises public health concerns. CHIKV infections cause fever and arthralgia, which can be debilitating and last for years. Here, we describe a CHIKV vaccine candidate based on trans-amplifying RNA (taRNA). The vaccine candidate consists of two RNAs: a non-replicating mRNA encoding for the CHIKV nonstructural proteins, forming the replicase complex and a trans-replicon (TR) RNA encoding the CHIKV envelope proteins. The TR-RNA can be amplified by the replicase in trans, and small RNA amounts can induce a potent immune response. The TR-RNA was efficiently amplified by the CHIKV replicase in vitro, leading to high protein expression, comparable to that generated by a CHIKV infection. In addition, the taRNA system did not recombine to replication-competent CHIKV. Using a prime-boost schedule, the vaccine candidate induced potent CHIKV-specific humoral and cellular immune responses in vivo in a mouse model. Notably, mice were protected against a high-dose CHIKV challenge infection with two vaccine doses of only 1.5 μg RNA. Therefore, taRNAs are a promising safe and efficient vaccination strategy against CHIKV infections. American Society of Gene & Cell Therapy 2022-05-02 /pmc/articles/PMC9126847/ /pubmed/35664702 http://dx.doi.org/10.1016/j.omtn.2022.04.036 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Schmidt, Christin Haefner, Erik Gerbeth, Julia Beissert, Tim Sahin, Ugur Perkovic, Mario Schnierle, Barbara S. A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title | A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title_full | A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title_fullStr | A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title_full_unstemmed | A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title_short | A taRNA vaccine candidate induces a specific immune response that protects mice against Chikungunya virus infections |
title_sort | tarna vaccine candidate induces a specific immune response that protects mice against chikungunya virus infections |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126847/ https://www.ncbi.nlm.nih.gov/pubmed/35664702 http://dx.doi.org/10.1016/j.omtn.2022.04.036 |
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