Title: Modulating Immune Responses to Control Virus Infection
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Human cytomegalovirus (HCMV) is a virus that spreads through saliva, blood, breast milk, and urine. Nearly everyone will be infected at some point in their life, and following this the virus lives inside them for their entire life. HCMV causes serious health complications and even death for those with weak immune systems, such as organ transplant recipients. It can also cause disease if it infects an unborn baby during pregnancy, leading to permanent disabilities such as intellectual disability, blindness, deafness, or even death. HCMV infection of babies is more common than other well-known conditions such as Downs syndrome, occurring in over 5,000 babies per year in the UK, and 44,000 per year in the USA. Drugs exist, but are toxic, are not licensed for use during pregnancy or in new-borns, and the virus can rapidly become resistant. As a result, better drugs are urgently needed. Key to the ability of the virus to cause disease is the fact that it hides from the immune system, and is never killed. In this proposal we will take two approaches to prevent this, so that the virus can be ‘seen’ and then killed by the immune system. Firstly, we will develop drugs that directly stop the virus from hiding. These would represent the first generation of a novel drug strategy. They would be effective, but people can suffer from multiple rounds of HCMV disease, and this drug would need to be given each time. Secondly, we will therefore identify ways of boosting the immune system so that it can control the virus permanently, without continually giving the drug. Being able to do this would produce a second generation drug, which would only need to be given at the beginning of infection.

Lay abstract: Human cytomegalovirus (HCMV) is a virus that spreads through saliva, blood, breast milk, and urine. Nearly everyone will be infected at some point in their life, and following this the virus lives inside them for their entire life. HCMV causes serious health complications and even death for those with weak immune systems, such as organ transplant recipients. It can also cause disease if it infects an unborn baby during pregnancy, leading to permanent disabilities such as intellectual disability, blindness, deafness, or even death. HCMV infection of babies is more common than other well-known conditions such as Downs syndrome, occurring in over 5,000 babies per year in the UK, and 44,000 per year in the USA. Drugs exist, but are toxic, are not licensed for use during pregnancy or in new-borns, and the virus can rapidly become resistant. As a result, better drugs are urgently needed. Key to the ability of the virus to cause disease is the fact that it hides from the immune system, and is never killed. In this proposal we will take two approaches to prevent this, so that the virus can be ‘seen’ and then killed by the immune system. Firstly, we will develop drugs that directly stop the virus from hiding. These would represent the first generation of a novel drug strategy. They would be effective, but people can suffer from multiple rounds of HCMV disease, and this drug would need to be given each time. Secondly, we will therefore identify ways of boosting the immune system so that it can control the virus permanently, without continually giving the drug. Being able to do this would produce a second generation drug, which would only need to be given at the beginning of infection.

Research activity codes: 5.1 PHARMACEUTICALS;5.2 CELLULAR AND GENE THERAPIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;INFECTION