DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice

Szurgot I, Hanke L, Sheward DJ, Vidakovics LP, Murrell B, McInerney GM, Liljeström P

Sci Rep 11 (1) 3125 [2021-02-04; online 2021-02-04]

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-S ecto). 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.

Category: Biochemistry

Category: Drug Discovery

Category: Vaccines

Funder: VR

Type: Journal article

PubMed 33542325

DOI 10.1038/s41598-021-82498-5

Crossref 10.1038/s41598-021-82498-5

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