A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains

van Doremalen, N.; Haddock, E.; Feldmann, F.; Meade-White, K.; Bushmaker, T.; Fischer, R.; Okumura, A.; Hanley, P.; Saturday, G.; Edwards, N.; Clark, M.; Lambe, T.; Gilbert, S.; Munster, V.

doi:10.1101/2020.04.13.036293

bioRxiv · 10.1101/2020.04.13.036293

A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains

van Doremalen, N.·Haddock, E.·Feldmann, F.·Meade-White, K.·Bushmaker, T.·Fischer, R.·Okumura, A.·Hanley, P.·Saturday, G.·Edwards, N.·Clark, M.·Lambe, T.·Gilbert, S.·Munster, V.

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Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans via the dromedary camel reservoir and can transmit between humans, most commonly via nosocomial transmission. Currently, no licensed vaccine is available. Previously we showed that vaccination of transgenic mice with ChAdOx1 MERS, encoding the MERS S protein, prevented disease upon lethal challenge. In the current study we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with ChAdOx1 MERS. Upon MERS-CoV challenge vaccinated animals were protected against respiratory injury and pneumonia and had a reduction in viral load in lung tissue of several logs. Furthermore, we did not detect MERS-CoV replication in type I and II pneumocytes of ChAdOx1 MERS vaccinated animals. A prime-boost regimen of ChAdOx1 MERS boosted antibody titers, and viral replication was completely absent from the respiratory tract tissue of these rhesus macaques. Finally, we investigated the ability of ChAdOx1 MERS to protect against six different MERS-CoV strains, isolated between 2012 to 2018, from dromedary camels and humans in the Middle East and Africa. Antibodies elicited by ChAdOx1 MERS in rhesus macaques were able to neutralize all MERS-CoV strains. Vaccination of transgenic hDPP4 mice with ChAdOx1 MERS completely protected the animals against disease and lethality for all different MERS-CoV strains. The data support further clinical development of ChAdOx1 MERS supported by CEPI. One Sentence SummaryPrime-only vaccination with ChAdOx1 MERS provides protective immunity against HCoV-EMC/2012 replication in rhesus macaques, and a wide variety of MERS-CoV strains in mice.

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van Doremalen, N., Haddock, E., Feldmann, F., Meade-White, K., Bushmaker, T., Fischer, R., Okumura, A., Hanley, P., Saturday, G., Edwards, N., Clark, M., Lambe, T., Gilbert, S., Munster, V.. 2020-04-13. A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains. https://doi.org/10.1101/2020.04.13.036293

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