Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model

Vincent J Munster,Emmie De Wit,Daniel Wright,Sarah C Gilbert,George M Warimwe,Trenton Bushmaker,Robert J Fischer,Daniel Wells,Teresa Lambe,Greg Saturday,Neeltje Van Doremalen

doi:10.1038/s41541-017-0029-1

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic virus that causes severe respiratory disease in humans with a case fatality rate close to 40%, but for which no vaccines are available. Here, we evaluated the utility of ChAdOx1, a promising replication-deficient simian adenovirus vaccine vector platform with an established safety profile in humans and dromedary camels, for MERS-CoV vaccine development. Using a transgenic lethal BALB/c MERS-CoV mouse model we showed that single dose intranasal or intramuscular immunisation with ChAdOx1 MERS, encoding full-length MERS-CoV Spike glycoprotein, is highly immunogenic and confers protection against lethal viral challenge. Immunogenicity and efficacy were comparable between immunisation routes. Together these data provide support for further evaluation of ChAdOx1 MERS vaccine in humans and dromedary camels, the animal reservoir of infection.

Highlights

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in Saudi Arabia in mid-20121 and as of March 2017 more than 1917 laboratory-confirmed cases with >650 related deaths had been officially reported to the World Health Organization (WHO)
Addressing this unmet need for MERS-CoV interventions has been prioritised by the WHO for urgent action[4] and could most rapidly be achieved through a one health approach in which products are codeveloped for use in humans and camels
ChAdOx1 MERS vaccination elicited neutralising antibodies with no statistically significant difference detected between immunisation routes (Mann Whitney U test, p = 0.49) (Fig. 1a)

Summary

Introduction

Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in Saudi Arabia in mid-20121 and as of March 2017 more than 1917 laboratory-confirmed cases with >650 related deaths had been officially reported to the World Health Organization (WHO). Ongoing disease control strategies have so far relied on minimising contact with dromedary camels, observing standard infection control measures to limit nosocomial transmission, contact tracing and quarantine. Addressing this unmet need for MERS-CoV interventions has been prioritised by the WHO for urgent action[4] and could most rapidly be achieved through a one health approach in which products are codeveloped for use in humans (to prevent disease) and camels (to limit virus shedding and block subsequent transmission to humans). Leveraging vaccine technology platforms with an established safety profile in both these target species would allow relatively rapid progression through the product development pipeline

Methods

Results

Conclusion