Scientists' search for a better MMR jab

A Trinity-based virologist has received substantial new research fundingto develop a measles, mumps and rubella vaccine with fewer side effects. Dick Ahlstrom reports

A dangerously large number of Irish parents have resisted repeated calls to have their children vaccinated against measles because of fears that the jab can cause serious side effects. Now a Dublin-based research team plans to develop a safer vaccine that might overcome these fears.

It is wrong for advocates of the three-in-one MMR vaccine to dismiss the fears as unfounded, argues Prof Greg Atkins, a virologist and director of the Moyne Institute of Preventative Medicine at Trinity College in Dublin. "The MMR vaccine project stems from the fact that there have been a number of adverse effects related to the vaccine," he says.

Autism is the biggest fear for parents, and despite the fact that repeated large-scale studies suggest the autism-MMR link does not exist, there are other side effects that make the development of a safer vaccine highly desirable, says Atkins.

The current MMR vaccine uses three live, attenuated - or weakened - viruses for measles, mumps and rubella. "The adverse effects come from the fact that they all use live viruses," says Atkins. Although the MMR vaccine currently in use does pose risks, he remains strongly in favour of vaccination. "The evidence of adverse effects for the wild-type virus are much worse, a thousand times or more than the vaccine," Atkins acknowledges. "Certainly you should be vaccinated, but there are adverse effects, which are well established, and nobody argues with them. Medical people tend to ignore them. What we are trying to get away from is the use of live viruses, because this has produced the risk."

To this end, Atkins and his team recently received a Science Foundation Ireland programme grant worth almost €700,000 for the development of a safer recombinant MMR vaccine. "This is part of a research programme that is now worth over €2 million that uses viral vaccines to treat human and animal diseases."

His approach is to use viral RNA to help stimulate a powerful and lasting immunity against the three diseases. "We are using recombinant RNA molecules. This isn't a DNA vaccine," he explains. "We are developing new technology to use naked RNA molecules as a vector to express the proteins produced by the measles, mumps and rubella viruses."

DNA resides in the nucleus and a DNA-based vaccine would have to carry out its action there, getting into the host genome and replicating itself to spark immunity. This it does by releasing messenger RNA that works inside the cell but outside the nucleus to produce viral proteins.

The Trinity group's approach is to use RNA instead. "It will not insinuate itself into the genome so it can't replicate," says Atkins. The recombinant messenger RNA is still capable of producing the same proteins as the live virus but has the added advantage of only achieving one round of protein production before breaking down.

The real challenge, however, is finding a way to get the RNA into enough cells to induce a sufficiently high level of immunity. Regular injection wouldn't reach enough cells and the RNA must be kept safely within a cell to do its work. It degrades rapidly outside the cell and "would be completely useless", Atkins says.

The National Microelectronics Research Centre at University College Cork has come up with an answer to this problem, known as "electroporation". "The electroporation is a new way of getting the RNA into the cells," says Atkins.

It involves delivering a very low-level electric shock at the point of injection. It is so small as to go unnoticed by the person receiving it, says Atkins, but it causes the cells briefly to become more porous, allowing the recombinant RNA to slip inside.

Once there, the messenger RNA performs more or less the same function as RNA released from the cell nucleus. The viral RNA is translated into a viral protein, a substance that the immune system recognises as foreign.

Atkins plans to include seven different RNA segments to spread the immune response across different forms of the three disease-causing organisms.

If everything works, the research should lead to a much safer vaccine with fewer side effects.

"This work is proof of principle," adds Atkins, but it will be a number of years before all the tests can be done to confirm safety.