ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models

Lambe, Teresa; Spencer, Alexandra J.; Thomas, Kelly M.; Gooch, Karen E.; Thomas, Stephen; White, Andrew D.; Humphries, Holly E.; Wright, Daniel; Belij-Rammerstorfer, Sandra; Thakur, Nazia; Conceicao, Carina; Watson, Robert; Alden, Leonie; Allen, Lauren; Aram, Marilyn; Bewley, Kevin R.; Brunt, Emily; Brown, Phillip; Cavell, Breeze E.; Cobb, Rebecca; Fotheringham, Susan A.; Gilbride, Ciaran; Harris, Debbie J.; Ho, Catherine M. K.; Hunter, Laura; Kennard, Chelsea L.; Leung, Stephanie; Lucas, Vanessa; Ngabo, Didier; Ryan, Kathryn A.; Sharpe, Hannah; Sarfas, Charlotte; Sibley, Laura; Slack, Gillian S.; Ulaszewska, Marta; Wand, Nadina; Wiblin, Nathan R.; Gleeson, Fergus V.; Bailey, Dalan; Sharpe, Sally; Charlton, Sue; Salguero, Francisco J.; Carroll, Miles W.; Gilbert, Sarah C.

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.