Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice

Author:

Spencer Alexandra JORCID,McKay Paul FORCID,Belij-Rammerstorfer SandraORCID,Ulaszewska MartaORCID,Bissett Cameron DORCID,Hu Kai,Samnuan Karnyart,Blakney Anna K.,Wright DanielORCID,Sharpe Hannah RORCID,Gilbride CiaranORCID,Truby Adam,Allen Elizabeth RORCID,Gilbert Sarah CORCID,Shattock Robin JORCID,Lambe TeresaORCID

Abstract

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

Publisher

Cold Spring Harbor Laboratory

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