PreprintCited by 246SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

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

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van Doremalen, Neeltje, Lambe, Teresa, Spencer, Alexandra, Belij-Rammerstorfer, Sandra, Purushotham, Jyothi N., Port, Julia R., Avanzato, Victoria, Bushmaker, Trenton +27 more·2020·bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 1,2 and is responsible for the COVID-19 pandemic 3 . Vaccines are an essential countermeasure urgently needed to control the pandemic 4 . Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

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Crossref · 10.1101/2020.05.13.093195

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  • LION/repRNA-CoV2S elicited modest but detectable T cell responses in macaques, consistent with previous studies of SARS-CoV-2 S-targeted DNA and live viral vector vaccines tested in nonhuman primates.

    “Our findings demonstrate that LION/repRNA-CoV2S elicited modest but detectable T cell responses in macaques (Fig. 5), an outcome that is consistent with previous studies of SARS-CoV-2 S-targeted DNA and live viral vector vaccines tested in nonhuman primates (53, 58).”
  • Humoral and cell-mediated immune responses have been associated with vaccine-induced protection against challenge or subsequent rechallenge after SARS-CoV-2 infection in a rhesus macaque model.

    “Humoral and cell-mediated immune responses have been associated with vaccine-induced protection against challenge18 or subsequent rechallenge after SARS-CoV-2 infection in a rhesus macaque model.19”

    From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [18]

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Authors
van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S., Purushotham, J. N., Port, J. R., Avanzato, V., Bushmaker, T., Flaxman, A., Ulaszewska, M., Feldmann, F., Allen, E. R., Sharpe, H., Schulz, J., Holbrook, M., Okumura, A., Meade-White, K., Pérez-Pérez, L., Bissett, C., Gilbride, C., Williamson, B. N., Rosenke, R., Long, D., Ishwarbhai, A., Kailath, R., Rose, L., Morris, S., Powers, C., Lovaglio, J., Hanley, P. W., Scott, D., Saturday, G., de Wit, E., Gilbert, S. C., & Munster, V. J.
Affiliations
  • University of Oxford (GB)
  • National Institute of Allergy and Infectious Diseases (US)
Corresponding author
  • Gilbert, Sarah C.
  • Munster, Vincent J.
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2020-05-13
OpenAlex
W3025110834
Cited by
246
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 18 · 2021: 88 · 2020: 133
Type
posted content
Language
en
Open access
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, public-domain)
Funders
  • National Institute for Health and Care Research
  • Department of Health and Social Care
  • National Institutes of Health (1ziaai001179-01)
  • Engineering and Physical Sciences Research Council (EP/R013756/1)
  • National Institute of Allergy and Infectious Diseases (1ZIAAI001179, 1ZIAAI001179-01)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
ChAdOx1 nCoV-19 vaccine, SARS-CoV-2, COVID-19 vaccines, adenovirus vector vaccine, rhesus monkeys, immunogenicity, humoral immune response, cell-mediated immunity, IgG subclasses, cytokine profiling, viral load, pneumonia prevention, spike protein

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