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Most of my work has been concerned with the presentation of Influenza antigens with class I molecules of the Major Histocompatibility complex. In the past we identified the major targets for T cells as the conserved nucleoprotein and matrix protein components of the virus and demonstrated that a system of cytosolic antigen presentation exists that passes peptides derived from these proteins into the ER where they bind to class I MHC molecules. With the recent pandemic this interest continues with a practical extension into the issue of whether heterotypic immunity (between pandemic strains) can be induced in man with live attenuated strains of influenza. We have developed our own design of live attenuated virus called S-FLU, that relies on mutations in the haemagglutinin signal sequence that are permissive for infection but prevent replication of the virus. The advantage of this approach is that all of the viral proteins are expressed in their appropriate context in the lung, and thus can induce a full set of local T and B cell responses. We are developing methods to deliver the vaccine virus by aerosol in collaboration with Ronan Mac Loughlin at Aerogen. Preliminary results in collaboration with Dr Kanta Subbarao (NIH) show that our vaccine viruses are capable of preventing illness caused by the most virulent forms of influenza in a murine and ferret infection model, and we are studying responses in the pig as a relevant large animal (in collaboration with Elma Tchillian, Pirbright). We are presently investigating the mechanisms of this immunity in the pig.
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medrxiv(2023)
Nature communicationsno. 1 (2023): 311-13
Frontiers in Immunology (2023): 1229051
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