As the number of cases of MERS, the Middle Eastern coronavirus, reaches 40 – with 20 deaths so far – the disease is behaving more and more like its relation, SARS, that killed nearly 800 people worldwide in 2003.
Although that death toll is scary, in some ways the similarity is a good thing: US fears that SARS could be used as a bioweapon mean research on the virus has continued, and one of the biggest hurdles to producing a safe vaccine – a wayward immune reaction – may have already been overcome. The hope is that what works for SARS may work for MERS.
SARS had a predilection for infecting healthcare workers and spreading in hospitals. The most recent MERS cases were in two healthcare workers in eastern Saudi Arabia, and the virus has also spread between people in hospital wards.
And like SARS, the MERS virus seems likely to pose problems for vaccine makers, says Peter Hotez of the Baylor College of Medicine in Houston, Texas, who last year formed a non-profit partnership to make a SARS vaccine.
Early efforts to make SARS vaccines, using whole, killed viruses or viral proteins, seemed promising. The vaccine candidates rapidly induced antibodies that, in cell culture, neutralised the virus. When vaccinated animals were exposed to SARS, the virus didn’t replicate in their lungs. But several labs noticed that the animals still experienced a lung inflammation resembling a severe allergy.
This rang alarm bells. Experimental vaccines for animal coronaviruses have had this effect, and it has also been seen with viruses from other families. Most notoriously, it occurred in the 1960s with vaccines for measles and respiratory syncytial virus (RSV), a common infection in babies. Vaccines containing killed viruses were tested in children and appeared safe, but when the children encountered live measles or RSV, they got sicker than unvaccinated children. Both vaccines were abandoned, and developers have been wary of the effect ever since.
Last year Robert Couch of Baylor College tested four experimental SARS vaccines in mice. All the vaccinated animals resisted infection, yet exposure to the SARS virus led to a severe lung inflammation similar to that seen with the RSV vaccine. The same thing, he reported, has been seen with many other experimental SARS vaccines.
The problem seems to be that rather than aiding the destruction of the invading virus, the antibodies switch sides. Malik Peiris of the University of Hong Kong found that antibodies to a vaccine made from the main surface protein of SARS allow the virus to enter immune cells, where they can trigger a destructive immune attack on the lung.
The good news is that only some parts of the SARS virus seem to cause this harmful effect. Studies by Shibo Jiang at Fudan University in Shanghai, China, and colleagues have found that the bit of the viral surface protein that attaches to a cell during infection – the binding site – only induces the right kind of antibody response. And the SARS vaccine that Hotez’s consortium plans to make is based on this binding site.
So what can this tell us about the ease or difficulty of producing a MERS vaccine? After all, MERS is not SARS – it binds to a different cell receptor, so the binding site is slightly different. However, work by Jiang’s team, submitted for publication, finds that the MERS binding site also induces strong antibodies which should not elicit the unwanted effect.
The binding site “is an excellent candidate for vaccine development”, says Chien-Te Tseng of the University of Texas Medical Branch at Galveston, who collaborated on Couch’s study of SARS vaccines. But careful testing will be needed to ensure it really doesn’t induce a harmful immune reaction, he says.
Jiang is now planning animal tests of his proposed MERS vaccine at the University of Hong Kong.
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