Project No. 2483

PRIORITY  PROJECT

Primary Supervisor

Dr Edward Wright – University of Sussex

Co-Supervisor(s)

Dr Ashley Otter –  UKHSA (CASE Partner)

Dr Ethan Morgan – University of Sussex

Summary

This study will improve our understanding of arboviral epidemiology and identify cross-reactive antibodies (Abs) and epitopes, which will inform public health strategies as well as vaccine and antiviral development targeting these viruses.

Arboviruses are transmitted via an arthropod vector. They can have severe consequences for animal and human health, causing hundreds of millions of cases each year, and cause a similar scale of economic losses to the global economy. Therefore, a greater understanding of the antigenicity of these viruses is needed to accelerate vaccine development.

To enable this, novel data regarding the immunogenicity and antigenicity of arboviruses, which are of high consequence to human and animal health, will be generated applied to the development of highly effective vaccine antigens. This will be achieved through the following objectives:

1. Develop and optimise immunoassays for high consequence arboviruses
Including functional assays, based on pseudotyped virus (PV) and viral replicon systems, as well as ELISAs and multiplexed binding assays (“Mosaic”). Receptor blocking assays, which provide a quasi functional-binding assessment of antibody (Ab) responses, will also be used.

2. Understand antibody cross-reactivity within genera and species
We will determine the breadth and potency of cross-reactive Abs stimulated by infection with one isolate against other isolates. This, coupled with bioinformatic analysis and published data, will inform the identification of broadly reactive epitopes that will be use to design highly effective vaccine antigens.

3. Assessing the impact of mutations on Ab immunity
Mutagenesis studies of the epitopes will be undertaken using phage deep mutational scanning, PV and replicon assays. Data from these experiments will enable us to predict the likely characteristics of future arbovirus variants with epidemic/pandemic potential.

This project would be suited to someone with experience and an interest in molecular biology, immunology and tissue culture.