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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Gilb, 2021. "Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23173-1
    DOI: 10.1038/s41467-021-23173-1
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    Cited by:

    1. Amy R. Rappaport & Sue-Jean Hong & Ciaran D. Scallan & Leonid Gitlin & Arvin Akoopie & Gregory R. Boucher & Milana Egorova & J. Aaron Espinosa & Mario Fidanza & Melissa A. Kachura & Annie Shen & Glori, 2022. "Low-dose self-amplifying mRNA COVID-19 vaccine drives strong protective immunity in non-human primates against SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Dennis Lapuente & Jana Fuchs & Jonas Willar & Ana Vieira Antão & Valentina Eberlein & Nadja Uhlig & Leila Issmail & Anna Schmidt & Friederike Oltmanns & Antonia Sophia Peter & Sandra Mueller-Schmucker, 2021. "Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Mai Komori & Takuto Nogimori & Amber L. Morey & Takashi Sekida & Keiko Ishimoto & Matthew R. Hassett & Yuji Masuta & Hirotaka Ode & Tomokazu Tamura & Rigel Suzuki & Jeff Alexander & Yasutoshi Kido & K, 2023. "saRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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