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Authors: Neeltje van Doremalen et al.

Link to paper: https://advances.sciencemag.org/content/early/2020/04/30/sciadv.aba8399/tab-e-letters

Journal/ Pre-Print: Science Advances

Tags: Vaccines

Research Highlights 

1. A single dose of ChAdOx1 MERS induces neutralising antibodies against MERS-CoV in rhesus macaques.

2. A single dose of ChAdOx1 MERS provides protection to rhesus macaques when challenged with MERS-CoV.

3. A single dose of ChAdOx1 MERS protects hDPP4-transgenic mice from 6 different MERS-CoV strains.

Summary

ChAdOx1 MERS is a simian adenovirus vectored vaccine encoding MERS-CoV S protein.

ChAdOx1 MERS induces MERS S-specific antibodies in rhesus macaques that neutralise up to 6 different strains of MERs-CoV. When challenged with MERS-CoV, rhesus macaques that had received one dose of ChAdOx1 MERS vaccine were protected against disease, i.e. had significantly less pulmonary pathology and lower clinical scores and viral RNA titers. A prime-boost regimen increased protection with even lower clinical scores and clearance of infectious virus in bronchoalveolar lavages by day 3 post-challenge.

In hDPP4-transgenic mice, ChAdOx1 MERS provided protection against 6 different strains of MERS.

This study offers a viable vaccine candidate against MERS-CoV, whose principles could be applied for a SARS-CoV2 vaccine.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV2/COVID19

· This study demonstrates that ChAdOx1 MERS provides protective efficacy against MERS-CoV in rhesus macaques. This suggests that the ChAdOx1 SARS-CoV2 vaccine currently in Phase 1 clinical trial might show protection in human.

Study Type

· In vivo study (e.g. mouse, NHP)

Strengths and limitations of the paper

Novelty: Describes ChAdOx1 MERS, a vaccine candidate that provides protection against MERS-CoV to rhesus macaques.

Standing in the field: This study is one of the first to evaluate a MERS-CoV vaccine in NHPs. It is the first study to demonstrate efficacy against MERS-CoV in NHPs following a single dose vaccination.

Appropriate statistics: The authors mostly use t tests but. Considering the small number of animals per group (N=6 macaques), tests that do not assume normality of the data such as non-parametric tests could be considered, too. Of note, the authors correct for multiple comparisons using a modified threshold for significance.

Viral model used: MERS-CoV strains HCoV-EMC/2012, Aseer/KSA-Rs924/62015, Korea/Seoul/SNU1-035/2015, Riyadh/KSA-18013832/2018, Camel/Burkina Faso/CIRAD-HKU785/2015, Camel/Saudi Arabia/KFU-HKU1/2013.

Translatability: This study demonstrates that ChAdOx1 MERS provides protective efficacy against MERS-CoV in rhesus macaques. This, along with previous evidence that ChAdOx1-vectored vaccines are safe in humans, suggests that ChAdOx1 MERS is a good vaccine candidate against MERS-CoV. Following on from the findings of this study and additional data, this group has started a ChAdOx1-vectored SARS-CoV2 vaccine trial.

Main limitations:

· The authors discuss blinding of the veterinary pathologist that interprets the histological images, but there doesn’t appear to be blinding of the researchers who determine the clinical score, which may be subjective.

· There are no experiments evaluating the safety of ChAdOx1 MERS in rhesus macaques in this study, which would be important to establish before this vaccine can enter clinical trials.