RT Journal Article
SR Electronic
T1 A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.13.036293
DO 10.1101/2020.04.13.036293
A1 Neeltje van Doremalen
A1 Elaine Haddock
A1 Friederike Feldmann
A1 Kimberly Meade-White
A1 Trenton Bushmaker
A1 Robert J. Fischer
A1 Atsushi Okumura
A1 Patrick W. Hanley
A1 Greg Saturday
A1 Nick J. Edwards
A1 Madeleine H.A. Clark
A1 Teresa Lambe
A1 Sarah C. Gilbert
A1 Vincent J. Munster
YR 2020
UL http://biorxiv.org/content/early/2020/04/13/2020.04.13.036293.abstract
AB 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 Summary Prime-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.Competing Interest StatementSCG is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines. The remaining authors declare no conflict of interest.