'SPIICA' - the Sao Paulo-Imperial College Immune Correlates in Arbovirus Infection Network

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The Aedes egypti mosquito can spread a number of different viruses. In regions of Brazil, these include the different types of Dengue virus, as well as Zika virus, Yellow fever virus and Chikungunya virus. Of these, perhaps the least is understood about Chikungunya. It is believed to be rather underdiagnosed. The symptoms can include headache, fever and rash. However, the key concern is that a proportion of patients will go on to develop a devastating arthritis-like, chronic disease which can continue for years. In some cases, disease is fatal. This is thus a disease which causes great misery to those infected and also, a great financial healthcare burden in caring for chronic disease. There is an urgent need to unravel why it is that some people experience mild disease, while others develop severe, chronic disease. It is believed that the chronic, joint disease is mediated not by the virus itself, but by the immune response to it. For this reason, there is an urgent need to understand the detailed aspects of protective host immunity, so reducing the risk that any future vaccines may inadvertently induce rather than prevent joint disease. To address this question, we here propose to build a joint centre of leading immunologists in England and Brazil. We have called the joint centre 'SPIICA', an astronomical allusion to two separate stars that appear as one. We will work closely together, including joint workshops and staff training. Central to the plan is to recruit a Chikungunya patient cohort, 90 patients in each of four groups, across three seasons at 6 clinical centres in Brazil. Each patient will be carefully evaluated clinically for Chikungunya symptoms and followed longitudinally, giving periodic blood samples. These blood samples will be evaluated using a large array of state-of-the art technologies, allowing correlations to be drawn between the immune response and the disease features. The approaches include characterisation of the antibody response to the virus, of the response by subsets of white blood cells including T lymphocytes and natural killer cells, and of immune mediators in the blood termed cytokines. Our aim is that, by the end of this study, we will have a much-improved rationale to explain the different outcomes following infection. This should help explain how to build vaccines that can promote protection without causing harm and also, how to predict who might be the patients who will develop the chronic disease, treating them before symptoms develop.