DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice
Abstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based...
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2021-02-01
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doaj-d1386101c6744298abd8dec1619e0d2b2021-02-07T12:37:37ZengNature Publishing GroupScientific Reports2045-23222021-02-0111111310.1038/s41598-021-82498-5DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in miceInga Szurgot0Leo Hanke1Daniel J. Sheward2Laura Perez Vidakovics3Ben Murrell4Gerald M. McInerney5Peter Liljeström6Department of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetAbstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.https://doi.org/10.1038/s41598-021-82498-5 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inga Szurgot Leo Hanke Daniel J. Sheward Laura Perez Vidakovics Ben Murrell Gerald M. McInerney Peter Liljeström |
spellingShingle |
Inga Szurgot Leo Hanke Daniel J. Sheward Laura Perez Vidakovics Ben Murrell Gerald M. McInerney Peter Liljeström DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice Scientific Reports |
author_facet |
Inga Szurgot Leo Hanke Daniel J. Sheward Laura Perez Vidakovics Ben Murrell Gerald M. McInerney Peter Liljeström |
author_sort |
Inga Szurgot |
title |
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice |
title_short |
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice |
title_full |
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice |
title_fullStr |
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice |
title_full_unstemmed |
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice |
title_sort |
dna-launched rna replicon vaccines induce potent anti-sars-cov-2 immune responses in mice |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-02-01 |
description |
Abstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2. |
url |
https://doi.org/10.1038/s41598-021-82498-5 |
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