ChAdOx1 nCoV-19 vaccine 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 coronavirus disease 2019 (COVID-19) pandemic 3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic 4. 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.
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Preclinical testing of mRNA-1273 and other SARS-CoV-2 vaccines in advanced clinical evaluation has shown a Th1-skewed vaccine response and no pathologic lung infiltrates.
“Of note, preclinical testing of mRNA-1273 and other SARS-CoV-2 vaccines in advanced clinical evaluation has shown a Th1-skewed vaccine response and no pathologic lung infiltrates. 15,26-28”
From Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine (2021) · cites this paper as [27]
The Abstract reports a predominantly Th1 response to ChAdOx1 nCoV-19 in mice, but a balanced Th1/Th2 response in rhesus macaques. The Pulmonary pathology and viral load section reports histologically normal lungs and no immune-enhanced inflammatory disease in vaccinated macaques. Thus this source supports the lung-pathology finding and a Th1-skewed response in mice, but not a Th1-skewed response in macaques or any finding about mRNA-1273. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPreclinical COVID-19 vaccine studies suggest that the development of neutralising antibody is associated with protection from subsequent challenge with live virus.
“Preclinical COVID-19 vaccine studies suggest that the development of neutralising antibody is associated with protection from subsequent challenge with live virus.50”
Several nonhuman primate COVID-19 vaccine studies are consistent with the possibility that COVID-19 vaccines prevent severe disease in humans but may not prevent upper respiratory tract infection.
“Several non-human primate COVID-19 vaccine studies are consistent with the possibility of COVDI-19 vaccines preventing severe disease in humans but possibly not preventing URT infection”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as van Doremalen et al., 2020
Multiple major candidate vaccines had efficacy at short-term protection in pre-clinical models, including the J&J Ad26 vector-based vaccine.
“Multiple major candidate vaccines had efficacy at short-term protection in pre-clinical models, including the J&J Ad26 vector-based vaccine”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as van Doremalen et al., 2020
Protection against lower respiratory tract infection (LRTI) may be easier to achieve than against upper respiratory tract infection (URTI).
“It has previously been shown that protection against lower respiratory tract infection (LRTI) may be easier to achieve than against upper respiratory tract infection (URTI), as challenge studies in rhesus macaques have shown stronger correlation between neutralizing titers and the level of subgenomic messenger RNA in bronchoalveolar lavage samples than in nasal swab samples 28 .”
From Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection (2021) · cites this paper as [28]
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- Authors
- van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S., Purushotham, J. N., Port, J. R., Avanzato, V. A., 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., Edwards, N. J., Wright, D., 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)
- National Institutes of Health (US)
- Corresponding author
- Gilbert, Sarah C.
- Munster, Vincent J.
- ORCID
- van Doremalen, Neeltje
- Lambe, Teresa
- Spencer, Alexandra
- Purushotham, Jyothi N.
- Port, Julia R.
- Avanzato, Victoria A.
- 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
- Edwards, Nick J.
- Wright, Daniel
- Bissett, Cameron
- Williamson, Brandi N.
- Rosenke, Rebecca
- Kailath, Reshma
- Morris, Susan
- Powers, Claire
- Lovaglio, Jamie
- Hanley, Patrick W.
- Scott, Dana
- Saturday, Greg
- de Wit, Emmie
- Gilbert, Sarah C.
- Munster, Vincent J.
- Venue
- Nature
- Published
- 2020-07-30
- Volume
- 586
- Issue
- 7830
- Pages
- 578-582
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8436420
- OpenAlex
- W3045724532
- Cited by
- 914
- References
- 17
- Citations by year
- 2026: 12 · 2025: 34 · 2024: 54 · 2023: 74 · 2022: 178 · 2021: 396 · 2020: 165
- FWCI
- 26.74
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-01-19)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute for Health and Care Research (COV19OxfordVaccine01)
- Department of Health and Social Care
- Home Office
- National Institutes of Health (1ZIAAIOO1179-01, 1ziaai001179-01, ZIA AI001179)
- Engineering and Physical Sciences Research Council (EP/R013756/1)
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases (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, adenoviral vector, spike protein, rhesus monkeys, pneumonia prevention, viral load, humoral immune response, cell-mediated immunity, T helper type 1 cells, Th2 cells, IgG subclasses, cytokines, prime-boost regimen, vaccine immunogenicity
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adenoviridae, Animals, Bronchoalveolar Lavage Fluid, Disease Models, Animal, Female, Immunoglobulin G, Immunity, Cellular, Lung, Macaca mulatta, Male, Pneumonia, Viral, Vaccination, Viral Vaccines, Cytokines, Coronavirus Infections, Th1 Cells, Viral Load, Mice, Immunity, Humoral, Pandemics, Spike Glycoprotein, Coronavirus
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