Harnessing the power of immunoinformatics: characterizing the role of T-cell immunity as an integral part of vaccine development and efficacy testing regimen
Aim: To characterize role of T-cell immunity as an integral part of vaccine development and efficacy testing
Method: SARS-CoV-2 genome data was curated from GISAID and annotated to identify variations in antigenic proteins (S, N, E and M) of SARS-CoV-2 isolates sequenced from the state of Maharashtra. T-cell epitope prediction algorithms and an in-house developed workflow was used to predict and identify HLA- class I potential binders and immunogens capable of generating CD8 T-cell response. Of the 1960 potential 9-mers,149 potential antigenic/immunogenic peptides were taken for validation. Docking simulations coupled with binding free energy studies helped to prioritize potential binders for respective HLA-class I alleles sampled in study cohort.
150 subjects from Maharashtra state were enrolled, i) 100 SARS-CoV-2 convalescent individuals having a positive RT PCR test (~30 days prior to enrolment) and ii) 50 vaccinated individuals having taken 2nd dose of SII-NVX-CoV2373 vaccine and completed at least 30 days post vaccination. To determine recognition of the predicted peptides PBMCs were utilised for performing in vitro ELISPOT assays. Prioritised peptides were observed to dock in the peptide-binding groove of HLA- class I molecules and generate significant immune response.
Results: This study helped to, a) correlate molecular interactions involved in conferring T-cell immunity with in-vitro studies characterising immune response at cellular level, b) characterize immune response generated via natural infection and vaccination using peptides identified by bio and immunoinformatics. Infected individuals showed epitope recognition to various peptides of SARS-CoV-2, with higher magnitude and breadth than vaccinated individuals. T-cell epitopes of spike and nucleocapsid proteins of SARS-CoV-2 exhibited higher recognition and therefore proved to be better candidates for characterizing CD8 T-cell immunity. The study validates that the Covishield vaccine is able to generate robust T cell immunity against various antigenic peptides of SARS-CoV-2 and the major variants of VoC and VoI that harbored mutations in anchor and/or HLA binding sites.
Conclusion: We demonstrate role of various molecular determinants in conferring CD8 T-cell immunity using bio and immunoinformatic approaches, the outcome of which is substantiated using in vitro assays.
