MERS-CoV candidate vaccine gears up for clinical trials
Posted: 22 June 2015 | Victoria White
Researchers from LMU have demonstrated the protective effect of a candidate vaccine directed against MERS-CoV in preclinical studies…
Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich have demonstrated the protective effect of a candidate vaccine directed against the coronavirus that causes Middle East Respiratory Syndrome (MERS-CoV) in preclinical studies.
Planning for the first clinical trial is now underway.
Currently, no protective vaccine is available against the coronavirus strain responsible for MERS. The need for such a vaccine is underlined by the current outbreak of the disease in South Korea, which has led to the infection of over 150 people and has already caused several deaths.
Two years ago, a team of researchers led by Professor Gerd Sutter reported that it had developed a candidate vaccine directed against the MERS-CoV. Further preclinical tests have confirmed its efficacy. These results lead the way for Phase I clinical trials, which will determine how well the vaccine is tolerated by human subjects.
MVA-MERS-S effectively induces protective immunity against MERS-CoV in a mouse model
The vaccine candidate, named MVA-MERS-S, is based on the use of a safety tested vaccine virus, the Modified Vaccinia virus Ankara (MVA). Essentially, MVA serves as a vehicle for an immunogenic antigen derived from the MERS-CoV. Using molecular biological techniques, Sutter’s team have altered the structure of the MVA genome in such a way that genetic information coding for proteins characteristic of other viral pathogens can be spliced into it. The modified virus is then able to synthesise the foreign protein and displays it on the surface of infected cells. Once there, it can be recognised by cells of the immune system, which are stimulated to produce antibodies and T cells against it. In this particular case, the researchers used this system to express the so-called spike glycoprotein (protein S) specific for MERS-CoV.
“We have now shown for the first time that MVA-MERS-S effectively induces protective immunity against MERS-CoV in a mouse model,” explains Dr Asisa Volz, a member of Professor Sutter’s group.
In earlier assays, the researchers had confirmed the immunogenicity of their candidate vaccine in a cell culture, and demonstrated that it elicits the production of protective levels of MERS-CoV-neutralising antibodies.
DIFZ has made a grant of EUR 1.5 million for a project investigating MVA-MERS-S
For the new study, the team used a mouse strain that had been genetically modified to make it susceptible to infection with MERS-CoV. Following immunisation with MVA-MERS-S, the mice were exposed to different doses of MERS-CoV. Subsequent tests revealed that, in mice that had received high doses of MERS-CoV, virus replication was markedly impaired, and the numbers of virus genomes in lung tissue were correspondingly reduced relative to the levels in non-immunised mice. “This demonstrates that our vaccine candidate is both safe and effective. Thus, there is no obvious risk that the resulting immune response might exacerbate rather than prevent the infection,” says Gerd Sutter.
MVA-MERS-S therefore meets important criteria for use in clinical tests on human subjects. Indeed, the German Centre for Infection Research (DIFZ) has already made a grant of approximately 1.5 million euros available for the project “GMP Manufacture and Phase I Clinical Investigation of MVA-MERS-S, an Experimental Prophylactic Vaccine against the Middle East Respiratory Virus Syndrome”, which will be led by Gerd Sutter.
Results from the preclinical studies are published in the Journal of Virology.
Middle East respiratory syndrome coronavirus (MERS-CoV)