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, Teresa Lambe, 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, Teresa Lambe
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.
Conflict of interest statement
S.C.G. is the co-founder and board member of Vaccitech (collaborators in the early development of this vaccine candidate), and is named as an inventor on a patent covering the use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. P.M.K. and R.J.S. are co-founders and R.J.S. is a board member of VaxEquity and VacEquity, and are named inventors on a patent application covering the SARS-CoV-2 saRNA vaccine candidate.
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Source: PubMed