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

Alexandra J. Spencer (), Paul F. McKay, Sandra Belij-Rammerstorfer, Marta Ulaszewska, Cameron D. Bissett, Kai Hu, Karnyart Samnuan, Anna K. Blakney, Daniel Wright, Hannah R. Sharpe, Ciaran Gilbride, Adam Truby, Elizabeth R. Allen, Sarah C. Gilbert, Robin J. Shattock and Teresa Lambe
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Alexandra J. Spencer: University of Oxford
Paul F. McKay: Imperial College London
Sandra Belij-Rammerstorfer: University of Oxford
Marta Ulaszewska: University of Oxford
Cameron D. Bissett: University of Oxford
Kai Hu: Imperial College London
Karnyart Samnuan: Imperial College London
Anna K. Blakney: Imperial College London
Daniel Wright: University of Oxford
Hannah R. Sharpe: University of Oxford
Ciaran Gilbride: University of Oxford
Adam Truby: University of Oxford
Elizabeth R. Allen: University of Oxford
Sarah C. Gilbert: University of Oxford
Robin J. Shattock: Imperial College London
Teresa Lambe: University of Oxford

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract Several 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.

Date: 2021
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DOI: 10.1038/s41467-021-23173-1

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