A Roadmap Towards the Identification and Validation of Conserved T Cell Epitope Regions in Viral Pathogen Families with Pandemic Potential.

Abstract

The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens. Examples of viral families considered and their respective prototypes (species/ subspecies) are Coronaviridae (Severe Acute Respiratory Syndrome-related Coronavirus/ SARS-CoV-2), Flaviviridae (Dengue virus/DENV2), Togaviridae (Chikungunya virus/ CHIKV), Paramyixoviridae (Morbillivirus/measles), Arenaviridae (Mammarenavirus/ Lassa), and Picornaviridae (Enterovirus C/poliovirus). The peptide sequences encoded in each prototype virus are then analyzed to determine their conservation across different viral taxonomic groups and viral variants derived from each of the VFPP. We outline available methodologies for epitope discovery based on panels of overlapping peptides and bioinformatics- based predictions of HLA-peptide binding, along with high-throughput in vitro assays, with emphasis on addressing coverage of the general worldwide population. Validation can be achieved by a variety of methodologies, including determining HLA restriction and recognition in samples from volunteers convalescent from previous infections or immunized with approved or experimental vaccines, and immunophenotyping of responding T cells. The capacity of these regions to induce crossreactive T cell responses can be tested experimentally with homologous peptides derived from the various viral species of interest. Importantly, they could be considered as a component of pan-viral family vaccines. Conversely, immunogenic regions that are highly specific to a given virus could be of interest for diagnostic applications.