Nine research teams are each receiving around £100,000 of seed-funding to help set up or improve volunteer infection studies for a range of different diseases. These awards aim to improve understanding of these diseases in order to accelerate vaccine development.
HIC-Vac's funding comes from the MRC, the Biotechnology and Biological Sciences Research Council (BBSRC), and the Global Challenges Research Fund (GCRF). The HIC-Vac network is directed by Professor Peter Openshaw and led from Imperial College London. The Deputy Director, Professor Andrew Pollard, is based at the University of Oxford.
The studies involve volunteers who are willing to participate in research that intentionally exposes them to a disease-causing microbes, including bacteria, viruses, and parasites. Teams of scientists can then study how the infection first takes hold to discover more about the early immune responses. This knowledge generated by volunteers can greatly accelerate the testing of new vaccines and treatments.
The funded projects are:
- Dr Roma Chilengi: Centre for Infectious Disease Research Zambia (CIDRZ), Zambia. “Characterisation of host immune responses to Salmonella Typhi in an endemic setting – a comparison of natural typhoid infection with controlled human infection.”
Typhoid is an infection caused by a bacterium called Salmonella typhi. It represents a major global health challenge with an estimated 11–20 million people getting sick from typhoid every year. Two typhoid vaccines are currently available for prevention of typhoid fever: however, neither is in routine use in Africa, partly because of poor efficacy and unsuitability for routine infant immunisation. Our goal is to characterise the immune response of Zambians naturally infected with typhoid and compare this to previous UK studies to support new vaccine development.
- Dr Roma Chilengi: Centre for Infectious Disease Research Zambia (CIDRZ), Zambia. “Development of a live attenuated rotavirus vaccine as a human infection challenge model.”
Rotavirus diarrhoea causes an estimated 215,000 infant deaths every year, most of which occur in Lower and Middle-income countries (LMICs). The widespread introduction of two WHO approved rotavirus vaccines has substantially reduced the number of deaths, but the vaccines are much less effective in babies born in LMICs compared to high-income countries. We are going to explore a study of the immune response of Zambian infants given a rotavirus vaccine using very gentle procedures (collecting saliva and stool samples). We hope this study is a step towards developing ways to find out if current vaccines can be made more effective and to test new vaccines.
- Dr Chris Chiu: Imperial College London, UK. “Human challenge with H3N2 influenza: an optimisation pilot study promoting collaboration.”
Influenza is still a major cause of death and disease worldwide. Every year up to 5 million people suffer severe infections and it causes around 500,000 deaths, many of which are in low and middle income countries (LMICs). Current vaccines are not very effective and need to be given annually, so there is a strong need to develop better ones. Researchers have been using volunteer infection studies for a long time to study influenza and test vaccines, but there is no standard way of carrying them out. We want to set out the best way to perform these studies, which will add scientific value by helping researchers directly compare data from different studies and share resources.
- Dr Jennifer Hill: University of Oxford, UK. “Antibody-mediated innate effector responses in human challenge models.”
Antibodies targeting bacteria, viruses and parasites are an important immune defence against infection, and many vaccines work by stimulating our body to make protective antibodies. But the precise ways in which they work is not fully understood. We want to gain a better understanding of which antibodies are important for different infections, and how they trigger an immune response that stops the infection in its tracks. This information could be key for developing new vaccines that generate a protective immune response.
- Dr Giorgio Napolitani: University of Oxford, UK. ‘Development of a platform to investigate the antigen specificity of CD4 T cell responses to respiratory pathogens.’
Streptococcus pneumoniae (the pneumococcus) is the most common bacterial cause of pneumonia and meningitis in children, and causes significant deaths in the elderly. There are two types of pneumococcal vaccine available in the UK, but there is an increasing incidence of pneumococcal disease that these vaccines don’t protect against. This combined with the emergence of antibiotic resistant strains makes the development of new generation vaccines against pneumococcus a global health priority. We are carrying out volunteer infection studies to find out more about a type of immune cell called a ‘T cell’ and how they recognise and respond to the bacteria. This approach could be used in future studies to identify new, more broadly protective vaccine candidates.
- Dr Meta Roestenberg: Leiden University Medical Center, The Netherlands. “Preparing for Schistosoma mansoni Controlled Human Infection Studies in Uganda.”
Schistosomiasis is a parasitic infection which affects 440 million people worldwide. There is only one drug is widely available to treat this infection, so we need new medicines and vaccines to prevent the infection. To accelerate their development, the Leiden University Medical Center are working with colleagues from the Uganda Virus Research Institute (UVRI) to set up a volunteer infection study in Uganda. It has been shown to be safe to experimentally infect healthy volunteers with this parasite in Leiden, monitoring the development of the worms using a new diagnostic test, and the next step is to establish the same study in Uganda to fast-track testing of novel vaccines and medicine for schistosomiasis.
- Dr Charles Sande: KEMRI-Wellcome Trust Research Programme, Kenya. “RESpiratory Proteomics In afRican and European subjects (RESPIRE).”
Respiratory Syncytial Virus (RSV) is the leading cause of childhood severe acute respiratory illness worldwide. All children will have been exposed to RSV by 2 years of age, but only 2% get seriously ill and the risk of death is disproportionally high for children from poor countries (where 99% of the RSV-linked deaths occur). The reason for the difference in the risk of serious illness and death in children is not well understood. Most RSV studies have involved healthy adult volunteers because of the ethical implications of studying infants, but we don’t know if adults (who are immune to RSV) respond the same way that infants do. We are looking at the protein response to natural RSV infection in adults and infants from different parts of the world. And comparing them to results from previous adult studies. This will provide valuable clues on the value of experimental adult infection as a tool for studying how disease happens in children.
- Dr Thushan De Silva: MRC Unit The Gambia at LSHTM. “Exploring mucosal molecular signatures associated with successful challenge with live attenuated influenza viruses.”
Live attenuated influenza vaccines (LAIV) contain weakened versions of flu viruses, which can infect people, but do not cause severe illness. Although primarily used for vaccination, they are also safe to be used to test how well other new vaccines work. This is particularly useful for helping understand flu infection in children, because LAIV is known to be very safe. We want to test a new non-invasive way to collect samples from children infected with LAIV to find out which of our genes are turned on and off in response to infection. Our goal is to gain insight into how influenza viruses interact with our immune system at the site of infection in a more detailed way than previously possible. These methods will not only be useful in the context of LAIV studies to accelerate vaccine development, but also more widely for other studies where infections are introduced into the nose.
- Dr Ryan Thwaites: Imperial College London. “Functional Characterisation of Mucosal Antibodies against Influenza (MUC-AB)”
During a viral chest infection, our bodies produce antibodies that help combat the virus and protect us from re-infection by the same virus. Vaccines protect against harmful infections by making use of this response to produce protective antibodies. Most vaccine studies look at levels of antibodies in the blood, but antibodies can also be found in our lungs and nose (called mucosal surfaces) where these infections occur – and these sites might be more important for vaccine efficacy. Our study will involve giving volunteers a flu vaccine so we can compare antibody levels in the blood, nose and lung surfaces and see how well the antibodies work. This project will enable us to study the antibody response at mucosal surfaces and understand how this might help to improve vaccines.
These are very exciting projects and we look forward to their impact – congratulations to the awardees.