Cross-reactive coronavirus immunity

Does immunity to previous infection with seasonal coronaviruses alter a person's outcome with SARS-CoV-2?

Theme Lead: Professor Mala Maini, Professor of Viral Immunology at University College London

Sub-theme Lead: Dr Thushan De Silva, University of Sheffield

SARS-CoV-2 is not the only coronavirus currently circulating in the UK – there are four seasonal coronaviruses (OC43, HKU1, 229E, and NL63) that usually cause mild to moderate upper-respiratory tract illnesses, like the common cold. Most people get infected with one or more of these viruses at some point in their lives. It is therefore important to understand how exposure to these other coronaviruses affects how you react to SARS-CoV-2, for example if it changes your likelihood of developing severe COVID-19, or gives you any kind of protection from the infection in the first place. Similarly, it is important to understand if immune responses triggered by SARS-CoV-2 remain able to recognise this virus if it mutates in places that help T cells recognise it.


There are three key issues to address within this theme:


1.  Characterise the extent and nature of T cell cross-reactivity in SARS-CoV-2 infection.

Researchers want to test whether T cell responses to seasonal (common cold) coronaviruses are able to cross-react with SARS-CoV-2. We will examine whether T cells in pre-pandemic samples that react to particular regions of seasonal coronaviruses expand in their function following in vitro and in vivo exposure to SARS-CoV-2. 


2.  If T cells for seasonal coronaviruses do react to SARS-CoV-2, and someone were exposed to seasonal coronaviruses before the pandemic, is the infection outcome different?

This aim will address whether T cells generated in response to a seasonal coronavirus infection are protective against SARS-CoV-2 infection. Capitalising on UK cohorts sampled prior to the pandemic (e.g. Born in Bradford and ALSPAC), we will assess whether people who have previously been exposed to one or more of the seasonal coronaviruses differ in their susceptibility to SARS-CoV-2.


3.  Do naturally arising viral variants allow SARS-CoV-2 to escape T cell recognition? (Led by Dr Thushan da Silva).

In close collaboration with COG-UK, any viral variants of SARS-CoV-2 circulating in the UK will be tested for their impact on known T cell recognition sites.  T cells that specifically react to SARS-CoV-2 will be tested to see how well they can recognise the virus despite mutations.


This theme will develop the technology and capability to define immune cross reactivity between different coronaviruses and to assess its clinical importance.


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Photo of Mala Maini
Professor Mala Maini, Theme 4 Lead