A new vaccine aims to train the immune system’s T cells to attack multiple strains of hepatitis C virus (HCV) at once, rather than just one. This matters because 180 million people worldwide—including 300,000 in the UK—are chronically infected with HCV. The virus exists as seven distinct genotypes and, within a single person, as a swarm of closely related variants. Current drug treatments are expensive, have severe side effects, and do not prevent re-infection. No vaccine exists for prevention or treatment. The researchers have already developed a vaccine that works against genotype-1, the dominant UK strain, but genotype-3 is equally prevalent in the UK. A vaccine that targets only one strain would leave half the infected population unprotected. If successful, the vaccine would target conserved regions of the virus—parts that remain the same across strains—making it effective against both genotype-1 and genotype-3 in the UK, and potentially against all seven genotypes globally. This could prevent the liver scarring, cirrhosis, and liver cancer that make HCV the most common reason for liver transplantation in the UK. The approach may also inform T-cell vaccines against other variable viruses such as HIV and hepatitis B.
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The aim of this research is to develop new vaccines against hepatitis C virus (HCV) infection. Importantly, our new vaccines will be effective against different strains of the virus. This is urgently needed as the global burden of HCV infection is immense with 180 million people infected world wide. Within the United Kingdom (UK) 300,000 people are infected. This may lead to liver scarring that progresses to cirrhosis, liver failure and liver cancer. HCV is now the most common reason for liver transplantation in the UK. There is currently no vaccine for either the prevention or the treatment of HCV, and the best available drug treatments are expensive, fraught with side effects, prolonged and frequently ineffective. New drug therapies are on the horizon, but these are only effective against some strains, may be associated with viral resistance, and do not protect against re-infection. Over centuries, HCV has evolved so that there are now 7 different major viral strains (genotypes) located in particular regions of the world. However, even within a single person, HCV exists as a swarm of closely related but different viruses. Within the UK the two major strains are genotype-1 and genotype-3. The equal prevalence of two genotypes within a country is a unique and special feature of the HCV epidemic in the UK. However, some parts of the virus are the same between strains -these are known as conserved regions. These regions may be the "Achilles heel" of the virus, since a vaccine that effectively targets conserved regions may protect against multiple strains. So far, we have developed a vaccine that we believe will protect against genotype-1 infection. The vaccine works by stimulating the immune system to make very high number of T cells that attack multiple parts of the virus. We know that T cells are important, since our earlier work showed that these cells are crucial in clearing HCV naturally after infection. Our vaccine is also able to stimulate immune responses in people that are already infected -although responses are weaker in this situation. In this way we hope to use the vaccine to both prevent and eradicate established infection. Now we plan to improve our T cell vaccine so that it works against different strains -and especially against both genotypes 1 and 3 in the UK. We will design the vaccine so that the T cells generated by the vaccine target regions that are conserved between viral regions. Once we have developed this, we can test and use the new vaccine in the UK where both genotypes-1 and -3 circulate. We also want to understand why some people respond better than others to vaccination. In addition, whilst we know a lot about the immune system and how it clears genotype-1 virus, we know very little about it clears genotype-3 virus. Understanding these things will allow us to develop new strategies to improve vaccines against HCV. The lessons that we learn in designing a T cell vaccine that is effective against multiple viral strains may also prove useful in combating other variable viruses like HIV and HBV. The research is being carried out by Dr. Ellie Barnes (Oxford University). She is collaborating closely with Okairos, a biotechnology company based in Italy, and several investigators from around the world. These collaborations draw together experts in the biology of T cells, vaccinology, and viral sequence analysis and uses new technologies to characterise T cells in great detail. We plan to use blood samples that we have collected from people who have been vaccinated with our vaccines to understand why some people respond better than others. We will design new vaccines against the conserved regions of multiple HCV strains using a database of thousands of HCV sequences that has been developed over the last decade. In this way we will develop a T cell vaccine against HCV that can be used throughout the world and prevent one of the major causes of liver disease.
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