An investigational vaccine called ChAdOx1 MERS protected two groups of rhesus macaques from disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV). This latest research of the MERS vaccine offers hope that we may be close to having a viable vaccine against MERS which has caused numerous deaths in the Middle East.
showing particles of the Middle East Respiratory
Syndrome Coronavirus that emerged in 2012
MERS-CoV is a relative of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19).
US National Institutes of Health scientists and colleagues are pursuing similar studies with ChAdOx1 SARS2, a vaccine candidate against SARS-CoV-2.
The researchers note that ChAdOx1 vaccines can be produced rapidly, have been shown to be safe in human patients. They suggest that the ChAdOx1 platform is ideal for the development of vaccines against novel emerging coronaviruses, such as SARS-CoV-2.
The findings of the ChAdOx1 MERS are published 10 June 2020 in the journal Science Advances – doi: 10.1126/sciadv. aba8399.
The researchers note that the clinical spectrum of MERS-CoV infection in humans varies from asymptomatic to severe respiratory disease and death. Patients present with influenza-like symptoms such as a fever and shortness of breath. Thereafter, they may develop pneumonia, which can require mechanical ventilation and support in an intensive care unit. Human to- human transmission of MERS-CoV is relatively limited and occurs mainly in nosocomial settings but has been reported in local communities as well.
Human cases of MERS-CoV were first reported in Saudi Arabia in 2012; dromedary camels are also infected with the virus and likely transmit it to people. Through January 2020, the World Health Organization had received reports of 2,519 MERSCoV cases and 866 deaths in 27 countries. It is mainly prevalent in the Arabian Peninsula, with the majority of cases (84%) occurring in Saudi Arabia.
ChAdOx1 MERS, which uses a replication- deficient chimpanzee adenovirus to deliver a MERS-CoV protein in recipients, also worked against six different strains of MERS-CoV when tested in mice as a single vaccination. Scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) led the project. Collaborators work at the University of Oxford in the United Kingdom; researchers at the University of Oxford Jenner Institute developed the ChAdOx1 vaccine technology.
Macaque study
In the macaque study, one group of animals was vaccinated 28 days prior to infection; the other group received two vaccinations – a prime-boost strategy – 56 and 28 days prior to infection. A third group of monkeys served as controls. The researchers report that none of the animals in the two treatment groups developed signs of MERS-CoV disease. The primeboost group clearly had less virus in lung tissue compared to the control group and no evidence of replicating virus, while the prime-only group showed much less virus in tissue than the control group. Both treatment groups showed no lung damage and were protected from disease, unlike the control animals.
The scientists’ MERS-CoV macaque study follows earlier studies of the experimental vaccine in mice. They also have successfully tested the vaccine platform against Nipah virus in hamsters and against Lassa virus in guinea pigs; they next plan to expedite testing a vaccine candidate against SARS-CoV-2.
The MERS vaccine is being studied in Phase 1 human clinical trials in the United Kingdom and Saudi Arabia. The same chimpanzee adenovirus vaccine platform also is being assessed for malaria, HIV, influenza, hepatitis C, tuberculosis and Ebola.
The researchers write: We recently demonstrated that vaccination of mice with a replication-deficient simian adenovirus vaccine vector (ChAdOx1) encoding fulllength MERS-CoV S protein (ChAdOx1 MERS) elicited high-titer MERS-CoVneutralizing antibodies and a robust CD8+ T cell response against the S protein. In addition, ChAdOx1 MERS vaccination resulted in full protection of human dipeptidyl peptidase 4 (hDPP4) transgenic mice against a lethal challenge with MERSCoV. ChAdOx1 MERS vaccination of dromedary camels was immunogenic and reduced MERS-CoV shedding after challenge in a highly stringent natural transmission model with multiday exposure to infectious MERS-CoV. ChAd-vectored vaccines against malaria, HIV, influenza, hepatitis C, tuberculosis , Ebola, and others show an excellent immunogenicity and safety profile in humans. In the current manuscript, we show that a single dose of ChAdOx1 MERS vaccine protects rhesus macaque model against a mucosal challenge with HCoV-EMC/2012. Serum obtained from vaccinated rhesus macaques was able to neutralize six diverse MERSCoV strains. Furthermore, a single dose of ChAdOx1 MERS vaccine protects hDPP4 transgenic mice against all evaluated MERS-CoV strains.
• doi: 10.1126/sciadv.aba8399
