Developing a next generation in vitro 3D immune organoids system for studying vaccine-induced immune response and immune-ageing across the life-course

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Vaccination is the most effective protection against infectious diseases, which relies on vaccine-induced immunity. All new vaccines need to be thoroughly tested for their protective immunity before their clinical use in humans. From the initial selection of vaccine candidates to pre-clinical testing of new vaccines for immunogenicity, it typically involves the use of a large number of animals. There is a great need for non-animal, laboratory-based methods to evaluate vaccine-induced immune responses including antibody response. We aim to develop an in vitro assay system that mimics human immune system and able to detect vaccine-induced immune responses, and therefore has the potential to replace or reduce the use of animals in vaccine testing. This may include the selection of vaccine candidates and batch testing, and mechanistic studies including immune ageing in humans.Vaccine-induced immunity against infection critically depend on adaptive immune system involving T and B cell activation and antibody response. The effects of ageing on immunity, including vaccine-induced immune responses, are also typically manifested in dysregulated function of T and B cells and antibody response. It is known ageing is generally associated with increased susceptibility to severe infection, including COVID-19 and influenza. An in vitro system enabling the cellular and molecular mechanistic studies on immune ageing, particularly at the early stage of immune senescence (i.e. the timing/age period it occurs) would have a big impact on understanding immune ageing to inform strategies against severe infection, and would help to reduce animal studies. Vaccine-induced immunity is typically tested by measurement of T cell response and antibody production which is produced in the secondary lymphoid tissues such as lymph nodes. Structurally similar to lymph nodes, adenoids and tonsils are lymphoid tissues located in the upper airway (nasopharynx), named nasopharynx-associated lymphoid tissue (NALT) and known to be the induction site for immunity against respiratory tract pathogens. We previously studied and demonstrated marked T cell and antibody responses in NALT immune cells of children and adults to a number of antigens and vaccines derived from some airway pathogens such as influenza. We therefore hypothesize that tonsillar immune cells could be used as a laboratory system to test vaccines, which will have an enormous potential to replace or reduce large numbers of animal experiments. In this project, we propose to take advantage of the availability of tonsillar tissues from routine elective surgery, to develop a lab method in test tube vaccine-induced immune responses. In collaboration with an industry partner with specific expertise in lab systems helping cell growth in 3D, we will use tonsillar cells to develop a next generation, animal-free cell culture system for testing vaccines, and also be able to study effect of aging on immunity in humans.