Optimal cellular assays for SARS-CoV-2 T cell, B cell and innate immunity - a consortium across 6 UK universities

Overview

Awarded under the UKRI NCSI4p COVID-19 Response scheme, the SOCA (SARS-CoV-2 Optimal Cellular Assays) Consortium brings together seven immunology research groups across the UK to optimise the rapid development of new approaches for measuring cellular immunity in COVID-19. Working as part of NCSI (Covid-19 National Core Studies in Immunology), the teams will develop complementary workstreams looking at new, small-scale tests that can be accessibly done with blood samples in a non-specialist setting.

At the beginning of the COVID-19 pandemic, surveillance of immunity to SARS-CoV-2 (the virus that causes COVID-19) was initially dominated by the development of tests to detect antibody responses to key antigens expressed by the virus. As the research focus has expanded to consider wider facets of cellular immunity to the virus, there is now a need to develop accessible tests that can also evaluate these parameters, especially T cell immunity, in exposed populations.

While many research findings have been reported, assays invariably depend on research-lab based, high-tech methodologies such as ELISpot (cell culture to count responding T cells with a coloured label) or flow cytometry (using lasers to detect activation of fluorescent-tagged cells). These are relatively hard to translate beyond a research setting and at high throughput as would be needed for a wider roll-out. The work undertaken by the SOCA Consortium will seek to develop novel strategies to bridge this gap.

The Consortium is led by Professor Danny Altmann (Imperial College London) and Professor Andrew Godkin (Cardiff University) in collaboration with researchers at Ulster University, the University of Oxford, the University of Surrey and the University of Southampton.

The research teams will work collaboratively with specific goals to address the following: 

  1. Ease of collection of assay samples
  2. Ease of assay operation beyond the research lab setting
  3. Optimised choice of pertinent immunogen(s) for
    1. the specific detection of SARS-CoV-2 
    2. the detection of immune responses specific for other seasonal  coronaviruses and
  4. immune responses that are x-reactive between SARS-CoV-2 and other seasonal coronaviruses.
  5. Validation of newly developed platforms against existing laboratory tests
  6. Potential to inform with respect to prevention of SARS-CoV-2 infection assessing protective immune status across B cell, T cell and innate populations.

Collaborators

Professor Rosemary Boyton and Professor Danny Altmann, Imperial College London

Will investigate the refashioning of their minimal peptide pool ELISpot to rapid analysis of stimulation in small, whole blood samples, analysed by Mass Spectroscopy proteomics time-course to derive novel, early, definitive markers of specific activation. they will collaborate with ICL bioengineering to translate analyte measurements into an accessible PoC test.

Dr David Gibson and Dr Priyank Shukla, Ulster University

Will be supported by the Nanotechnology and Integrated Bioengineering Centre (NIBEC) at Ulster University and FlexMedical Solutions Ltd, with expertise in rapid device prototyping and assay chemistry development. The team has been developing a blood sampling device, BloodTrackR, which could act as a platform for isothermal amplification of target transcript and electrochemical detection for fast, cost-effective analysis of finger lancet blood samples.

Professor Andrew Godkin and Dr Martin Scurr, Cardiff University and ImmunoServ Ltd.

Will develop a standardisable (ELISA-based) whole blood assay to detect specific T cells in high-throughput format amenable to population-scale studies, with a rapid turnaround. In partnership with ImmunoServ, the aim will be a validation cohort study involving repeat analysis of the initial 100 subjects, 100 healthcare workers and a further 200 participants

Professor Eleanor Barnes, Oxford University

Will identify T cell epitopes that are specific for SARS-CoV-2 or specific for seasonal HCoVs or cross-reactive. Generate HLA-I/HLA-II pentamers for rapid detection of responses, then optimise a whole blood stimulation assay

Professor Susanna Dunachie, Oxford University

Will assess a novel memory T-cell-derived lactate assay to determine SARS-CoV-2 responses – a non-FLOW based assay detecting SARS-CoV-2 specific proliferation. The assay is cheap and scalable.

Professor Deborah Dunn-Walters, University of Surrey

Will assess the viability of RNA-based PCR tests for determination of memory B cell durability and investigate dielectrophoresis and other biosensor methods of assessing B cell memory responses.

Professor Salim Khakoo and Dr Marta Polak, University of Southampton

Will develop assays for innate immunity (NK cells, monocytes/dendritic cells. The first phase will focus on target identification for innate cellular assays, preliminary analysis of targets, and in the second phase will seek to collaborate to develop near-patient assays - lab-on-a chip, or paper-based assays with the SME Highfield Diagnostics.