March 2010 - Swinburne University of Technology

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swinburne March 2010 health 18 Dr Lara Grollo Synthetic vaccine hope Photo: Paul Jones in fight against polio successor Research is stepping up into the development of synthetic vaccines, which are potentially safer, cheaper and more practical than conventional biological vaccines By Julian Cribb Worldwide, an insidious virus is on the march, causing paralysis and death in very young children. It hasn’t yet created banner headlines, but for medical researchers such a disturbing combination of symptoms has not been seen since the great polio epidemics of the early 20th century. The virus is called EV71 and in most cases only causes a mild infection, known as ‘hand, foot and mouth disease’, which causes fever, blisters and rashes. But unpredictably and mysteriously some outbreaks turn lethal: the virus invades the person’s central nervous system, causing paralysis in babies and meningitis in children aged between two and four years. Western Australia experienced an acute outbreak of EV71 in 1999, which led to 14 cases of meningitis and eight of paralysis. More recently epidemics have occurred in Japan, Singapore, Malaysia, Korea and Taiwan, while almost half a million cases were reported in China over a four-month period in 2009. Outbreaks are seasonal, usually occurring in summer and autumn, and may claim the lives of 10 to 15 per cent of infants infected.
March 2010 swinburne Key points In most cases EV71 causes a mild infection, known as hand, foot and mouth disease, which causes fever, blisters and rashes Some outbreaks turn lethal, with the virus invading the central nervous system, causing paralysis in babies and meningitis in children aged 2 to 4 years Swinburne is working to ,, develop a safe vaccine and antiviral treatment Normal vaccines made from an attenuated, or killed, virus are effective – but they have drawbacks. For this reason we are taking the approach of trying to develop a synthetic peptide vaccine.” Dr Lara Grollo The virus is now in the sights of Swinburne University of Technology’s Dr Lara Grollo and her team, which is working to develop a safe vaccine and antiviral treatment. If successful, it will end the crippling, unpredictable run of EV71 and make it as much a part of history as its close relative, poliovirus. “At present there is no effective antiviral therapy or vaccine available for EV71 in the world. Washing hands and using clean water remain our best defence against it,” Dr Grollo says. “It’s been around a long time, and we are probably seeing more of it now because the western world has largely eradicated polio.” Like polio, EV71 normally lives in the gut and is spread through poor hygiene. Inexplicably, some outbreaks develop the capacity to invade the central nervous system and cause brain fever and paralysis. This is what makes the development of a safe vaccine so important. “Normal vaccines made from an attenuated, or killed, virus are effective – but they have drawbacks. For this reason we are taking the approach of trying to develop a synthetic peptide vaccine. “These are easy to purify, cheap to produce in large quantities and you don’t have to keep them in a fridge, which is a big advantage in the developing world or remote areas. Importantly, too, there is no risk the vaccine constituents can revert to diseasecausing organisms.” Using sophisticated computer modelling, the team is carefully searching the proteins that make up the coat of the virus for small molecular sequences known as peptides, which could prime the immune system of vaccine recipients or be used as an antiviral drug to block the virus’s ability to infect. This in itself is a sizeable challenge, because EV71 has many strains. Whatever the team comes up with has to be effective in protecting people against all of them. The idea is for fragments of viral material to be copied synthetically. Ideally, these copies will still be enough to prime the body’s white blood cells, generating an immune response every time the immunised person encounters the virus. “Conveniently, all strains have the same number and type of proteins in their coats but the sequences of the proteins have minor differences. We are looking for tiny parts of those proteins which are conserved across all the different strains of the virus, and are capable of triggering an immune response,” Dr Grollo explains. Her team’s search for a global vaccine against EV71 is showing promise. Several peptides have been identified that appear able to halt a viral infection in the laboratory. The next step is to extend the research to live trials in mice. “The in vitro work tells us we can obtain an immune response and create antibodies to the virus. To establish how protective it will be, we need to go to the next stages of testing it in animals and, eventually, in human clinical trials.” While other groups around the world are searching for a vaccine against EV71, Dr Grollo’s Swinburne team is the only group using an approach to exploit the cutting-edge technology of synthetic peptides. So far, she explains, no synthetic peptide vaccines against viral diseases have yet been licensed for use in humans, but there are several in phase II and III human trials. “The beauty of this approach is that, because you are only using chemical copies of small fragments of the virus’s coat proteins, it is much less likely to provoke a negative response in the recipient. It is also cheap and easy to manufacture, and remains much more stable than a normal vaccine – you can even store it in powdered form and dissolve it in liquid when you want to administer it.” Synthetic peptide vaccines may also do away with another unpleasant aspect of vaccination – needles – and rather be inhaled through the nose in a fine spray. Dr Grollo’s team’s careful investigation of the proteins of the virus’s coat also opens up the possibility of developing new ways to actually attack EV71 – by developing drugs that will specifically target and bind to sites in both virus and patient where the virus ‘docks’ and so prevent infection. If successful, this would provide medical workers with a second weapon for controlling outbreaks by directly treating infected patients. Like polio, EV71 is a horrifying virus that every year kills or paralyses thousands of babies and young children worldwide. But Dr Grollo is convinced that, like polio, it can be beaten – and that among her most promising peptides she will find the tools to end the scourge. •• Contact. . Swinburne University of Technology 1300 275 788 magazine@swinburne.edu.au www.swinburne.edu.au/magazine health 19 CAN YOU SQUEEZE 4,000,000 COPIES OF THIS MAGAZINE ONTO DISC? Swinburne can. And now the team at our Centre for Micro Photonics are working on their next challenge; technology that will allow the contents of as many as 200,000 DVDs to be stored on a single disc. You can read all about it, and many more fascinating breakthroughs, when you subscribe to the online version of this magazine. It’s a mere 2.5 megabytes in size, and free to subscribe. QUESTION EVERYTHING 1300 275 788 swinburne.edu.au/magazine CRICOS Provider: 00111D
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March 2010 - Swinburne University of Technology

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