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DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice
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- Szurgot, I (author)
- Karolinska Institutet
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- Hanke, L (author)
- Karolinska Institutet
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- Sheward, DJ (author)
- Karolinska Institutet
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- Liljestrom, P (author)
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- (creator_code:org_t)
- 2021-02-04
- 2021
- English.
- In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 3125-
- Journal article (peer-reviewed)
Abstract
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- 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.
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