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Biography
Jack is a postdoctoral scientist working as part of the PRRS Immunology Group at The Pirbright Institute, under Professor Simon Graham. Jack graduated in microbiology from the University of Surrey, and recently obtained his doctorate from the University of Oxford, focussing on recombinant protein and monoclonal antibody engineering to deepen the understanding of the porcine reproductive and respiratory syndrome virus (PRRSV).
Jack's current focus is as part of an international consortium of scientists and commercial partners aiming to develop a bivalent vaccine and companion diagnostic test for Nipah virus (NiV) and Pseudorabies virus (PrV), specialising in recombinant protein engineering and generation. Research interests
Use of protein and antibody engineering to identify subdominant, converseved epitopes as targets for potential therapeutics Projects you're working on
A high human fatality rate and broad host tropism makes NiV a serious public and animal health concern. The development of a human NiV vaccine has been prioritised. The development of a NiV vaccine for pigs would represent another tool to prevent and/or contain NiV outbreaks. However, limited marketability presents a significant challenge. We therefore propose the development of a bivalent PrV-NiV vaccine. Live attenuated PrV are highly effective vaccines and excellent vectors for foreign antigens (Dong et al., 2014; Jiang et al., 2007). We constructed and evaluated PrV expressing soluble forms of both NiV prefusion stabilised (Pre)F and G proteins. Pigs mounted immune responses comparable to the parental PrV vaccine and to protective NiV vaccine candidates. In this project, we aim to construct a novel version of this vaccine candidate that we hypothesise will augment immune responses to NiV glycoproteins and enable protection after a single immunisation. We will engineer NiV G and PreF with transmembrane domains so that they will be expressed on the surface of PrV-infected cells. Repetitive presentation of viral antigens is a key factor to increasing the robustness of B cell responses (Caradonna and Schmidt, 2021). We will determine whether this strategy improves immunogenicity. We will then evaluate the most immunogenic construct's ability to protect against virulent PrV and NiV. Thus, we will generate critical proof-of-concept for PrV expressing NiV glycoproteins to function as a bivalent vaccine. We will initiate studies to provide the vaccine with an additional competitive advantage over existing PrV vaccines. We will evaluate the thermostabilisation of the vaccine candidate by ensilication, a method that encases proteins in a protective silica cage has been shown to physically prevent the thermal denaturation of proteins outside cold chain (Wahid et al, 2019). Our previous studies have shown that ensilication cages prevent vaccine denaturation and preserves potency outside cold chain (Doekhie et al, 2020). We will convert a the NiV N protein-based DIVA diagnostic test to a lateral flow format, more appropriate for field use in the NiV endemic region. Discipline
Immunology – B-cells Molecular biology Structural biology Virology Host species
Pigs Zoonoses Pathogen
Bacteria Viruses›Arteriviruses Viruses›Herpesvirus Viruses›Nipah virus Viruses›Porcine reproductive and respiratory syndrome virus Stage of vaccine development
Antigen discovery and immunogen design