Investigating how early coronavirus exposure(s) drives protective COVID-19 immunity

A 2025 Crick PhD project with Emma Wall & David Bauer.

Vaccine-induced immunity to respiratory viruses, including SARS-CoV-2 wanes, necessitating regular boosting to provide enduring protection to at-risk adults from hospitalisation and death. However, despite ongoing viral evolution, COVID-19 remains a mild illness for the majority of the global population for whom vaccine boosters are frequently unavailable, but where infection exposures provide additional ‘hybrid’ immunity. 

This studentship aims to interrogate the development of hybrid immunity against SARS-CoV-2, testing if prior exposure to seasonal and animal/bat coronaviruses contributes to early, pre-vaccine humoral and T-cell mediated immunity against SARS-CoV-2 variants, including omicron. You will have access to a rich bioresource of samples from participants in the three parallel longitudinal prospective cohort studies across three different geographical regions with differing vaccine uptake, disease severity and variant evolution– West Africa1,2, West Indies3 and West London4,5, as part of a unique Crick-led collaboration WWW, funded by the Wellcome Trust. 

This project will involve a combination of wet-lab & dry-lab analysis with the aim of examining three possible determinants that may shape immunity to emerging SARS-CoV-2 variants: 

• History of antigenic exposure to SARS-CoV-2: both the initial exposure and subsequent exposures with mutations in key epitopes
• Cross-reactive prior immunity to other bat and human coronaviruses
• Genetic factors associated with immune breadth (together with Ed Carr).

You will have access to longitudinal data including genotyping, cellular immune profiling, conventional ELISA, and the Crick’s high-throughput live virus neutralising antibody assay collected across our three cohorts between 2020-2024. The project focuses on interrogating prior antigen exposures across the three cohorts using Phage Immunoprecipitation Sequencing (PhIP-seq). You will work in concert with members of the Bauer Lab, the UCLH-Crick Legacy Study, the COVID-19 Surveillance Unit (Mary Wu), Crick’s Bioinformatics and Biostatistics STP and our collaborators in the WWW Consortium to use PhIP-Seq describe and compare the repertoire of early exposures in our three parallel cohorts and how exposure associates with immune breadth. You will integrate these data with our extensive resources, including clinical metadata to develop models testing how different early exposures inform subsequent immunity. 

Candidate background

The ideal candidate will have a background in virology, molecular biology, bioinformatics or natural sciences, with an undergraduate degree in biochemistry or biological sciences. This project will suit a candidate with prior post-graduate experience either on the experimental side (PhIP-Seq, molecular virology including phage work, serology), or on the computational side (data analysis, modelling e.g. using R/Stan) — and be comfortable working collaboratively to learn the “other side” of their project.