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

van Doremalen, Neeltje; Lambe, Teresa; Spencer, Alexandra; Belij-Rammerstorfer, Sandra; 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; 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.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. 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.