Cellular immunity and resistance to schistosomiasis in the Philippines Schistosomiasis, also known as bilharzia or snailfever, is a parasitic worm infection currently infecting more than 200 million people worldwide. Infection remains a major health risk in the Philippines, with an estimated 2 million Filipinos infected and 12 million of the population at risk of infection. Humans are infected though contact with fresh water, such as rice paddies and streams, where the snails carrying the parasite live. Once inside the human host the adult worms produce eggs, which get stuck in the liver and other organs where they evoke inflammation and blockages. No vaccine is currently available and despite attempts to control the infection with mass drug treatment programs, low-grade chronic infections leading to anaemia, growth retardation and cognitive impairment are still prevalent. Re-infection occurs quickly even after treatment since the parasite is still widespread in water sources which people need to access.  The overall aim of this proposal is to assess the role of various types of immune cells in the development of resistance or susceptibility to schistosome reinfection, with a long term goal to support vaccine development. Previous studies have shown that individuals that have high levels of a particular type of antibody (IgE) in their blood are more resistant to becoming reinfected with schistosomiasis after drug treatment, whilst individuals with a different type of antibody (IgG4) are more susceptible to becoming reinfected. However, what is not known is what type of immune cells and mediators are involved in controlling what kind of antibodies are generated in different people. In order to develop effective vaccines against schistosomiasis, we need to have a better understanding of how protective, as well as non-protective immune responses are generated in naturally infected humans. This proposal aim to address this gap in knowledge by analysing immune function correlates of protection and susceptibility in individuals living in a schistosome endemic area of the Philippines. Antibodies are produced by B cells but various types of T cells are important in instructing the B cells in what kind of antibodies they should produce. We are particularly interested two specific types of T cells, known as follicular T helper cells (Tfh) and follicular T regulatory cells (Tfr), as well as the mediators they produce, in order to determine whether these particular cells are responsible for influencing the antibody classes produced during infection. We hypothesise that an individual's Tfh and Tfr numbers and phenotypes are crucial in determining if they become resistant or susceptible to reinfection. No previous studies have investigated the interaction between Tfh, Tfr and B cells in schistosomiasis and the new information gathered from this study will be of great importance for the ability to develop the vaccine needed to combat this debilitating disease in the Philippines and other parts of the world. Schistosomiasis is a major public health problem and a barrier to social and economic development in the resource poor areas of the Philippines. Our application will promote advancement in biotechnology and health sciences that will impact public health in the Philippines and globally. Our proposal also has the added benefit of potentiating both the international mobility of Filipino researchers and the establishment of sustainable global scientific partnerships. Collectively, these advances in scientific understanding and in capacity building will provide a framework for tackling barriers to development and for nurturing progress, with Filipino investigators being key drivers in change. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.