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

• Published in: Nature (London) Vol. 586; no. 7830; pp. 578 - 582
• Main Authors: van Doremalen, Neeltje, Lambe, Teresa, Spencer, Alexandra, Belij-Rammerstorfer, Sandra, 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, Gilbride, Ciaran, Williamson, Brandi N., Rosenke, Rebecca, Long, Dan, Ishwarbhai, Alka, Kailath, Reshma, Rose, Louisa, Morris, Susan, Powers, Claire, Lovaglio, Jamie, Hanley, Patrick W., Scott, Dana, Saturday, Greg, de Wit, Emmie, Gilbert, Sarah C., Munster, Vincent J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.10.2020; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/31; 13/51; 14/63; 631/326/590; 631/326/596/4130; 64/60; Adenoviridae - genetics; Alveoli; Analysis; Animal models; Animals; Betacoronavirus - immunology; Bronchoalveolar Lavage Fluid; Bronchus; Clinical trials; Control; Coronavirus Infections - genetics; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; Coronavirus Infections - virology; Coronaviruses; COVID-19; COVID-19 Vaccines; Cytokines; Cytokines - immunology; Diagnosis; Disease Models, Animal; Female; Health aspects; Helper cells; Humanities and Social Sciences; Immune response; Immune response (cell-mediated); Immune response (humoral); Immune system; Immunity, Cellular; Immunity, Humoral; Immunogenicity; Immunoglobulin G; Immunoglobulin G - immunology; Lung - immunology; Lung - pathology; Lung - virology; Macaca mulatta - immunology; Macaca mulatta - virology; Male; Mice; Middle East respiratory syndrome; multidisciplinary; Pandemics; Pandemics - prevention & control; Pneumonia; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Pneumonia, Viral - virology; Respiratory diseases; Respiratory tract; Rhesus monkey; Rodents; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Testing; Th1 Cells - immunology; Vaccination; Vaccines; Viral diseases; Viral Load; Viral pneumonia; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2608-y

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. The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals.