Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice
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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.
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- Authors
- 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.
- Affiliations
- University of Oxford (GB)
- Imperial College London (GB)
- Corresponding author
- Spencer, Alexandra J.
- ORCID
- Venue
- Nature Communications
- Published
- 2021-05-17
- Volume
- 12
- Issue
- 1
- Pages
- 2893-2893
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8129084
- OpenAlex
- W3160352759
- Cited by
- 125
- References
- 22
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 14 · 2023: 16 · 2022: 44 · 2021: 42
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- UK Research and Innovation (MC_PC_19055)
- National Institute for Health and Care Research (COV19 OxfordVacc-01, COVID-19, OxfordVacc-01, COV19OxfordVaccine01, MC_PC_19055)
- University of Oxford
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- heterologous vaccination, self-amplifying RNA vaccine, adenovirus vector vaccine, SARS-CoV-2, COVID-19 vaccines, prime-boost vaccination, antibody response, neutralizing antibodies, cell-mediated immunity, cytotoxic T lymphocytes, Th1 cells, immunogenicity
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, ChAdOx1 nCoV-19, Animals, Antibodies, Viral, Immunization, Secondary, RNA, Viral, T-Lymphocytes, Cytotoxic, Vaccination, Vaccines, Synthetic, Th1 Cells, Mice, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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