An AI platform to facilitate the rapid development of T cell based diagnostic tests: applied to SARS-CoV-2

During 2022, NOI has continued to repurpose the NEC Immune profiler (NIP), to enable it to profile the SARS-CoV-2 virus and other pathogens to identify good immunogenic T cell targets. In addition, NOI has been working on developing other pipelines and statistical tools, which leverage the predictions from the repurposed NIP and work in tandem with the human population modelling “digital twin” tool developed earlier in the project. This enables the AI-platform to identify hotspot combinations (and constitutive epitopes) that are cross-reactive against different members of a viral species or a broader viral genus, and simultaneously provide broad coverage in the human population. This facilitates the design of blueprints for diagnostics and vaccines that not only work for specific viral species but can provide broad coverage against emerging variants of concern or other related viral species. In parallel, OUS has developed a more refined flow-based - activation-induced maker - assay, to further characterize the SARS-VoV-2 test peptides identified earlier in the project using the NIP prediction engine. OUS has identified and validated a subset of these peptides that stimulated robust CD4+ and CD8 + T cell recall responses in PBMCs from both SARS-CoV-2 convalescent individuals and immunized donors. Finally, these peptides were used to screen cohorts of high-risk immunocompromised patients for vaccine generated CD8+ T cell immune responses. This data has been shared with the Norwegian Institute of Public Health (NIPH) and the Norwegian government and helped shape vaccination guidelines and policy for high-risk immunocompromised patients. The data also clearly demonstrates the utility of the NIP identified peptides in a diagnostic setting.

Main outcomes: (1) During the project, NOI has successfully developed the AI platform described the project application, and the platform has been validated by OUS in terms of identifying relevant immunogenic T cell targets for developing diagnostics in the context of SARS-CoV-2. NOI has also established a new infectious disease business unit, which will focus on leveraging the AI-platform to screen pathogenic genomes and rapidly develop diagnostic and vaccine blueprints. (2) During the project, OUS has identified a subset of peptides that have the potential to be further developed into a robust diagnostic test to identify patients with T cell immunity to SARS-CoV-2. These peptides are currently being used by OUS to screen cohorts of high-risk immunocompromised patients for vaccine generated CD8+ T cell immune responses. This data has been shared with the Norwegian Institute of Public Health (NIPH) and the Norwegian government and helped shape vaccination guidelines and policy for high-risk immunocompromised patients. However, the rapid development and deployment of the COVID-19 vaccines, their general acceptance as an "immunity passport", has reduced the market need for a new commercially available T cell based diagnostic test for COVID-19. Consequently, NOI is currently focusing the technology on opportunities within the vaccine space such as the development of a prophylactic pan beta-coronavirus vaccine and a therapeutic vaccine against the hepatitis B virus (HBV). Main impacts: (1) The AI platform developed in this project can facilitate the rapid development of novel diagnostics and vaccines against new waves of COVID-19, and/or new emerging diseases, as evidenced in this project. The AI platform has gained significant traction with key international players in the infectious disease field such as CEPI and Shionogi. CEPI recently awarded NOI with funding of USD 4.8m to use the AI platform to design and develop a broadly protective pan beta-coronavirus vaccine with OUS and the European Vaccine Initiative as sub-awardees. In addition, NOI has entered into a collaboration with Shionogi to design a therapeutic vaccine against chronic HBV. (2) An effective pan beta-coronavirus vaccine would protect the human population from new SARS-CoV-2 variants of concern and any new beta-coronavirus emerging in the human population from a future spillover event, alleviating the otherwise significant health and socio-economic costs.

It has been over a century since we encountered a pandemic like COVID-19. The rate of global transmission and the associated morbidity and mortality have been both shocking and devastating. The pandemic has sparked fears of a chronic worldwide recession or depression. Shut-downs, social distancing and travel restrictions have destroyed many jobs and businesses. A reliable diagnostic test to quantify whether citizens have been infected or have recovered from the virus is critical to overcome this crisis. A proposal that is gaining increasing traction is the use of diagnostic tests to generate immunity passports—i.e., certification that a citizen is immune to SARS-CoV-2. Citizens in possession of an immunity passport could then return to work and travel, thereby reigniting the economy. However, as governments gear up efforts to establish immunity passports based on antibody tests, there is a significant risk that these passports will be denied to immune individuals. Recent studies suggest that only 50% of convalescent COVID-19 patients have a detectable antibody response as their infection has been controlled and eradicated by the cellular arm of their immune system driven by T cells. It is therefore critical to develop diagnostic tests that can quantify cellular immunity towards SARS-CoV-2. In this project NEC OncoImmunity (NOI) will work with our partner Professor Ludvig Munthe at the Oslo University Hospital (OUS) to develop a T-cell diagnostic to complement the antibody tests. NOI will use artificial intelligence (AI) and bioinformatics methods to select the viral peptides that can be used to identify T-cells that provide immunity against COVID-19, which will be subsequently validated using COVID-19 biobanks and T-cell assays developed by Professor Ludvig Munthe’s group. The AI platform developed in the project will guide the development of a novel T cell-based diagnostic for COVID-19 and facilitate the introduction of reliable immunity passports.