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

I løpet av 2022 har NOI fortsatt arbeidet med å gjenbruke NEC predikeringsplattformen, NEC "Immune profiler" (NIP), for å profilere SARS-CoV-2 viruset og andre patogener, og identifisere gode immunogene T-celle mål. I tillegg har NOI jobbet med å utvikle andre plattformer og statistiske verktøy, som benytter predikeringer fra NIP og fungerer i tandem med verktøyet digital tvillingsanalyse, som ble utviklet tidligere i prosjektet for å modellere HLA-mangfoldet i den humane populasjonen. Dette gjør det mulig for AI plattformen å identifisere hotspot-kombinasjoner (og konstitutive epitoper) som er kryssreaktive på tvers av virustyper innen samme virale familie, og som samtidig har høy dekningsgrad i den totale humane populasjonen. Dette muliggjør design av blåkopier for ny diagnostikk og vaksiner som ikke bare fungerer mot spesifikke virus, men som kan gi bred beskyttelse mot nye varianter eller andre beslektede virustyper. Parallelt har OUS utviklet en raffinert «flow-based-activation-induced» markøranalyse, for å ytterligere karakterisere SARS-CoV-2 testpeptidene som ble identifisert tidligere i prosjektet ved hjelp av NIP predikeringsplattformen. OUS har identifisert og verifisert et subsett av disse peptidene som stimulerte robust CD4+ og CD8+ T celle «recall» respons i PBMCer fra både SARS-CoV-2 rekonvalesente individer og immuniserte donorer. Til sist, ble disse peptidene benyttet til å screene for vaksinegenerert CD8+ T-celle immunrespons i kohorter bestående av høy-risiko immunkomprimerte pasienter. Dataene er delt med Folkehelseinstituttet og norske helsepolitikere, og har bidratt til å endre retningslinjer for vaksinering av høyrisiko immunkomprimerte pasienter. Dataene viser også tydelig nytten av NIP til å identifisere peptider som kan benyttes i en diagnostisk 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.