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ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques

Author

Listed:
  • Neeltje van Doremalen

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Teresa Lambe

    (University of Oxford)

  • Alexandra Spencer

    (University of Oxford)

  • Sandra Belij-Rammerstorfer

    (University of Oxford)

  • Jyothi N. Purushotham

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
    University of Oxford)

  • Julia R. Port

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Victoria A. Avanzato

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Trenton Bushmaker

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Amy Flaxman

    (University of Oxford)

  • Marta Ulaszewska

    (University of Oxford)

  • Friederike Feldmann

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Elizabeth R. Allen

    (University of Oxford)

  • Hannah Sharpe

    (University of Oxford)

  • Jonathan Schulz

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Myndi Holbrook

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Atsushi Okumura

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Kimberly Meade-White

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Lizzette Pérez-Pérez

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nick J. Edwards

    (University of Oxford)

  • Daniel Wright

    (University of Oxford)

  • Cameron Bissett

    (University of Oxford)

  • Ciaran Gilbride

    (University of Oxford)

  • Brandi N. Williamson

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Rebecca Rosenke

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Dan Long

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Alka Ishwarbhai

    (University of Oxford)

  • Reshma Kailath

    (University of Oxford)

  • Louisa Rose

    (University of Oxford)

  • Susan Morris

    (University of Oxford)

  • Claire Powers

    (University of Oxford)

  • Jamie Lovaglio

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Patrick W. Hanley

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Dana Scott

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Greg Saturday

    (National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Emmie de Wit

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Sarah C. Gilbert

    (University of Oxford)

  • Vincent J. Munster

    (Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime–boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.

Suggested Citation

  • Neeltje van Doremalen & Teresa Lambe & Alexandra Spencer & Sandra Belij-Rammerstorfer & Jyothi N. Purushotham & Julia R. Port & Victoria A. Avanzato & Trenton Bushmaker & Amy Flaxman & Marta Ulaszewsk, 2020. "ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques," Nature, Nature, vol. 586(7830), pages 578-582, October.
    • Handle: RePEc:nat:nature:v:586:y:2020:i:7830:d:10.1038_s41586-020-2608-y
    DOI: 10.1038/s41586-020-2608-y
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    Citations

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    Cited by:

    1. Robert J. Fischer & Neeltje van Doremalen & Danielle R. Adney & Claude Kwe Yinda & Julia R. Port & Myndi G. Holbrook & Jonathan E. Schulz & Brandi N. Williamson & Tina Thomas & Kent Barbian & Sarah L., 2021. "ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. 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.
    3. Neeltje van Doremalen & Jonathan E. Schulz & Danielle R. Adney & Taylor A. Saturday & Robert J. Fischer & Claude Kwe Yinda & Nazia Thakur & Joseph Newman & Marta Ulaszewska & Sandra Belij-Rammerstorfe, 2022. "ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. 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.
    5. Ankita Leekha & Arash Saeedi & K M Samiur Rahman Sefat & Monish Kumar & Melisa Martinez-Paniagua & Adrian Damian & Rohan Kulkarni & Kate Reichel & Ali Rezvan & Shalaleh Masoumi & Xinli Liu & Laurence , 2024. "Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Jaclyn A. Kaiser & Christine E. Nelson & Xueqiao Liu & Hong-Su Park & Yumiko Matsuoka & Cindy Luongo & Celia Santos & Laura R. H. Ahlers & Richard Herbert & Ian N. Moore & Temeri Wilder-Kofie & Rashid, 2024. "Mucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Eakachai Prompetchara & Chutitorn Ketloy & Mohamad-Gabriel Alameh & Kittipan Tharakhet & Papatsara Kaewpang & Nongnaphat Yostrerat & Patrawadee Pitakpolrat & Supranee Buranapraditkun & Suwimon Manopwi, 2023. "Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Marco Mandolesi & Hrishikesh Das & Liset Vries & Yiqiu Yang & Changil Kim & Manojj Dhinakaran & Xaquin Castro Dopico & Julian Fischbach & Sungyong Kim & Mariia V. Guryleva & Monika Àdori & Mark Cherny, 2024. "Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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