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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...

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Autores principales: Schmidt, Christin, Haefner, Erik, Gerbeth, Julia, Beissert, Tim, Sahin, Ugur, Perkovic, Mario, Schnierle, Barbara S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
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.
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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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