ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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).”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A new coronavirus associated with human respiratory disease in China
Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2008-3 · Cited by 11,688 · see citing works
Virological assessment of hospitalized patients with COVID-2019
Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2196-x · Cited by 6,661 · see citing works
Development of an inactivated vaccine candidate for SARS-CoV-2
Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., Li, Y., Zhu, L., Wang, N., Lv, Z., et al. (2020) · Science · doi:10.1126/science.abc1932 · Cited by 1,434 · see citing works
Flagged first, then by citations
Research works printed but not linked: 11
- [1]Zhu N. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 382, 727– 733, doi: 10.1056/NEJMoa2001017 (2020). 31978945 PMC7092803 · DOI · Paper page
- [4]Lurie N., Saville M., Hatchett R. & Halton J. Developing Covid-19 Vaccines at Pandemic Speed. N Engl J Med, doi: 10.1056/NEJMp2005630 (2020). 32227757 · DOI · Paper page
- [5]van Doremalen N. A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques. Science Advances, doi: 10.1126/sciadv.aba8399 (2020). PMC7286676 32577525 · DOI
- [6]Munster V. J. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature, doi: 10.1038/s41586-020-2324-7 (2020). PMC7486227 32396922 · DOI · Paper page
- [8]Weingartl H. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol 78, 12672– 12676, doi: 10.1128/JVI.78.22.12672-12676.2004 (2004). 15507655 PMC525089 · DOI
- [9]Bolles M. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol 85, 12201– 12215, doi: 10.1128/JVI.06048-11 (2011). 21937658 PMC3209347 · DOI · Paper page
- [10]Liu L. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 4, doi: 10.1172/jci.insight.123158 (2019). PMC6478436 30830861 · DOI · Paper page
- [11]Dicks M. D. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS One 7, e40385, doi: 10.1371/journal.pone.0040385 (2012). 22808149 PMC3396660 · DOI
- [12]Bewig B. & Schmidt W. E. Accelerated titering of adenoviruses. Biotechniques 28, 870– 873, doi: 10.2144/00285bm08 (2000). 10818691 · DOI
- [13]Maizel J. V. Jr., White D. O. & Scharff M. D. The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7A, and 12. Virology 36, 115– 125, doi: 10.1016/0042-6822(68)90121-9 (1968). 5669982 · DOI
- [14]Corman V. M. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill 25, doi: 10.2807/1560-7917.ES.2020.25.3.2000045 (2020). PMC6988269 31992387 · DOI
Cited by
Sorted by citations
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., Diemert, D., Spector, S. A., Rouphael, N., Creech, C. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035389 · Cited by 10,119 · see citing works
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., McCullough, M. P., Chappell, J. D., Denison, M. R., Stevens, L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022483 · Cited by 3,237 · see citing works
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419 · see citing works
Wang, H., Zhang, Y., Huang, B., Deng, W., Quan, Y., Wang, W., Xu, W., Zhao, Y., Li, N., Zhang, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.008 · Cited by 748 · see citing works
A thermostable mRNA vaccine against COVID-19
Zhang, N.-N., Li, X.-F., Deng, Y.-Q., Zhao, H., Huang, Y.-J., Yang, G., Huang, W.-J., Gao, P., Zhou, C., Zhang, R.-R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.024 · Cited by 671 · see citing works
Immunological mechanisms of vaccine-induced protection against COVID-19 in humans
Sadarangani, M., Marchant, A., & Kollmann, T. R. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00578-z · Cited by 560 · see citing works
REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters
Baum, A., Ajithdoss, D., Copin, R., Zhou, A., Lanza, K., Negron, N., Ni, M., Wei, Y., Mohammadi, K., Musser, B., et al. (2020) · Science · doi:10.1126/science.abe2402 · Cited by 517 · see citing works
Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
Juno, J. A., Tan, H.-X., Lee, W. S., Reynaldi, A., Kelly, H. G., Wragg, K., Esterbauer, R., Kent, H. E., Batten, C. J., Mordant, F. L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0995-0 · Cited by 437 · see citing works
Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality
Zohar, T., Loos, C., Fischinger, S., Atyeo, C., Wang, C., Slein, M. D., Burke, J., Yu, J., Feldman, J., Hauser, B. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.052 · Cited by 297 · see citing works
Erasmus, J. H., Khandhar, A. P., O’Connor, M. A., Walls, A. C., Hemann, E. A., Murapa, P., Archer, J., Leventhal, S., Fuller, J. T., Lewis, T. B., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9396 · Cited by 241 · see citing works
Immunological imprinting of the antibody response in COVID-19 patients
Aydillo, T., Rombauts, A., Stadlbauer, D., Aslam, S., Abelenda-Alonso, G., Escalera, A., Amanat, F., Jiang, K., Krammer, F., Carratala, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23977-1 · Cited by 223 · see citing works
Rauch, S., Roth, N., Schwendt, K., Fotin-Mleczek, M., Mueller, S. O., & Petsch, B. (2021) · npj Vaccines · doi:10.1038/s41541-021-00311-w · Cited by 165 · see citing works
A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2
Tai, W., Zhang, X., Drelich, A., Shi, J., Hsu, J. C., Luchsinger, L., Hillyer, C. D., Tseng, C.-T. K., Jiang, S., & Du, L. (2020) · Cell Research · doi:10.1038/s41422-020-0387-5 · Cited by 151 · see citing works
Adenovirus vector-based vaccine for infectious diseases
Sakurai, F., Tachibana, M., & Mizuguchi, H. (2022) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100432 · Cited by 148 · see citing works
The Mechanism of SARS-CoV-2 Nucleocapsid Protein Recognition by the Human 14-3-3 Proteins
Tugaeva, K. V., Hawkins, D. E. D. P., Smith, J. L. R., Bayfield, O. W., Ker, D.-S., Sysoev, A. A., Klychnikov, O. I., Antson, A. A., & Sluchanko, N. N. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166875 · Cited by 95 · see citing works
Who should be prioritised for COVID-19 vaccination?
Russell, F. M., & Greenwood, B. (2021) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2020.1827882 · Cited by 75 · see citing works
Kim, J., Mukherjee, A., Nelson, D., Jozic, A., & Sahay, G. (2020) · doi:10.1101/2020.07.24.205583 · Cited by 28 · see citing works
- 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.
- ORCID
- Lambe, Teresa
- Spencer, Alexandra
- Purushotham, Jyothi N.
- Port, Julia R.
- Avanzato, Victoria
- Bushmaker, Trenton
- Flaxman, Amy
- Ulaszewska, Marta
- Feldmann, Friederike
- Allen, Elizabeth R.
- Sharpe, Hannah
- Schulz, Jonathan
- Holbrook, Myndi
- Okumura, Atsushi
- Meade-White, Kimberly
- Pérez-Pérez, Lizzette
- Bissett, Cameron
- Williamson, Brandi N.
- Rosenke, Rebecca
- Kailath, Reshma
- Morris, Susan
- Powers, Claire
- Lovaglio, Jamie
- Hanley, Patrick W.
- Scott, Dana
- Saturday, Greg
- Gilbert, Sarah C.
- Munster, Vincent J.
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2020-05-13
- PMC
- PMC7241103
- 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
- green
- doi.org
- Licence
- public-domain
- creativecommons.org/publicdomain/zero/1.0/ (vor)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review