Identifying new T-cell targets for SARS-CoV-2 and pan-coronavirus vaccination

SARS-CoV-2 belongs to a large family of viruses termed coronaviruses. In 2019, the virus crossed over into human circulation causing the COVID-19 pandemic, making SARS-CoV-2 the seventh established human coronavirus (HCoV). Current SARS-CoV-2 vaccine strategies have so far been successful in reducing infection rates and fatalities associated with the COVID-19 pandemic. However, vaccine target Spike is prone to mutation, which has led to the evolution of variants of concern that can escape vaccine induced immunity. An even higher degree of mutation can be seen across HCoVs. It is also worth noting that three HCoVs have emerged in the last 20 years, suggesting research is needed to prepare for possible emergence of another. Thus, the aim of this project is to find a vaccine target that is relatively unmutated across current HCoVs that would consequently also likely remain unmutated in future HCoV; to achieve pan-coronavirus protection. For this work, the focus will be on the 16 non-structural proteins (NSPs). NSPs collectively all contribute to virus replication and so are fundamental for virus survival and less commonly mutated in

To achieve this, we will assess the T-cell response of recently infected individuals to peptides derived from regions of SARS-CoV-2 NSPs that are well conserved across HCoVs. Following this, we will further characterise the T-cell response to these conserved regions through generation and use of NSP-specific T-cell clones. We will then assess the ability of these T-cell clones to recognise and control a SARS-CoV-2 infected cell, as well as cells infected with different HCoVs. Collectively, this data will allow assessment of whether targeting of NSPs will enable protection against SARS-CoV-2, as well as achieve pan-coronavirus protection.