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Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice.
Nat Commun. 2021 05 17; 12(1):2893.NC

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.

Authors+Show Affiliations

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK. alex.spencer@ndm.ox.ac.uk.Department of Infectious Disease, Imperial College London, London, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Department of Infectious Disease, Imperial College London, London, UK.Department of Infectious Disease, Imperial College London, London, UK.Department of Infectious Disease, Imperial College London, London, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.Department of Infectious Disease, Imperial College London, London, UK.Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34001897

Citation

Spencer, Alexandra J., et al. "Heterologous Vaccination Regimens With Self-amplifying RNA and Adenoviral COVID Vaccines Induce Robust Immune Responses in Mice." Nature Communications, vol. 12, no. 1, 2021, p. 2893.
Spencer AJ, McKay PF, Belij-Rammerstorfer S, et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat Commun. 2021;12(1):2893.
Spencer, A. J., McKay, P. F., Belij-Rammerstorfer, S., Ulaszewska, M., Bissett, C. D., Hu, K., Samnuan, K., Blakney, A. K., Wright, D., Sharpe, H. R., Gilbride, C., Truby, A., Allen, E. R., Gilbert, S. C., Shattock, R. J., & Lambe, T. (2021). Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nature Communications, 12(1), 2893. https://doi.org/10.1038/s41467-021-23173-1
Spencer AJ, et al. Heterologous Vaccination Regimens With Self-amplifying RNA and Adenoviral COVID Vaccines Induce Robust Immune Responses in Mice. Nat Commun. 2021 05 17;12(1):2893. PubMed PMID: 34001897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. AU - Spencer,Alexandra J, AU - McKay,Paul F, AU - Belij-Rammerstorfer,Sandra, AU - Ulaszewska,Marta, AU - Bissett,Cameron D, AU - Hu,Kai, AU - Samnuan,Karnyart, AU - Blakney,Anna K, AU - Wright,Daniel, AU - Sharpe,Hannah R, AU - Gilbride,Ciaran, AU - Truby,Adam, AU - Allen,Elizabeth R, AU - Gilbert,Sarah C, AU - Shattock,Robin J, AU - Lambe,Teresa, Y1 - 2021/05/17/ PY - 2021/01/28/received PY - 2021/04/19/accepted PY - 2021/5/18/entrez PY - 2021/5/19/pubmed PY - 2021/5/29/medline SP - 2893 EP - 2893 JF - Nature communications JO - Nat Commun VL - 12 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/34001897/Heterologous_vaccination_regimens_with_self_amplifying_RNA_and_adenoviral_COVID_vaccines_induce_robust_immune_responses_in_mice_ L2 - https://doi.org/10.1038/s41467-021-23173-1 DB - PRIME DP - Unbound Medicine ER -