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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
Nature, 10/2020, Volume: 586, Issue: 7830Journal Article
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic . Vaccines are an essential countermeasure and are urgently needed to control the pandemic . 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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