Mapping the immunopeptidome of seven SARS-CoV-2 antigens across common HLA haplotypes
Most COVID-19 vaccines elicit immunity against the SARS-CoV-2 Spike protein. However, Spike protein mutations in emerging strains and immune evasion by the SARS-CoV-2 virus demonstrates the need to develop more broadly targeting vaccines. To facilitate this, we use mass spectrometry to identify immunopeptides derived from seven relatively conserved structural and non-structural SARS-CoV-2 proteins (N, E, Nsp1/4/5/8/9). We use two different B-lymphoblastoid cell lines to map Human Leukocyte Antigen (HLA) class I and class II immunopeptidomes covering some of the prevalent HLA types across the global human population. We employ DNA plasmid transfection and direct antigen delivery approaches to sample different antigens and find 248 unique HLA class I and HLA class II bound peptides with 71 derived from N, 12 from E, 28 from Nsp1, 19 from Nsp4, 73 from Nsp8 and 45 peptides derived from Nsp9. Over half of the viral peptides are unpublished. T cell reactivity tested against 56 of the detected peptides shows CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses against several peptides from the N, E, and Nsp9 proteins. Results from this study will aid the development of next-generation COVID vaccines targeting epitopes from across a number of SARS-CoV-2 proteins.
Authors
- Patricia T. Illing (ORCID: https://orcid.org/0000-0002-3870-0796)
- Katherine Kedzierska (ORCID: https://orcid.org/0000-0001-6141-335X)
- Jan Petersen (ORCID: https://orcid.org/0000-0002-2045-6342)
- Kirti Pandey (ORCID: https://orcid.org/0000-0003-0799-6376)
- Thi H. O. Nguyen (ORCID: https://orcid.org/0000-0002-9294-7693)
- Nathan P. Croft
- Gry Persson
- Nicole A. Mifsud
- Louise C. Rowntree (ORCID: https://orcid.org/0000-0002-0649-5089)
- Sri H. Ramarathinam (ORCID: https://orcid.org/0000-0002-2787-1282)
- Asolina Braun
- Michael Schantz Klausen (ORCID: https://orcid.org/0000-0003-2225-5701)
- Emma J. Lange
- Shanzou Chung
- Dene R. Littler (ORCID: https://orcid.org/0000-0001-5904-1905)
- Pouya Faridi (ORCID: https://orcid.org/0000-0002-2712-3356)
- Ziyi Huang (ORCID: https://orcid.org/0000-0002-1678-3463)
- Jens Vindahl Kringelum (ORCID: https://orcid.org/0000-0002-7415-3283)
- Katherine E. Scull (ORCID: https://orcid.org/0000-0003-4042-7685)
- Jamie Rossjohn (ORCID: https://orcid.org/0000-0002-2020-7522)
- Anthony W. Purcell (ORCID: https://orcid.org/0000-0003-0532-8331)
- Rochelle Ayala (ORCID: https://orcid.org/0000-0001-8538-8857)
- Nikolas Thuesen
- Shabana Raji (ORCID: https://orcid.org/0009-0006-1499-6664)
- Chen Li (ORCID: https://orcid.org/0000-0002-1847-754X)
- Anders Bundgård Sørensen
Institutions
- The University of Melbourne (AU)
- Discovery Institute (US)
- Australian Regenerative Medicine Institute (AU)
- ExpreS2ion Biotechnologies (Denmark) (DK)
- Peter Doherty Institute (AU)
- Monash University (AU)
- Cardiff University (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1038/s41467-024-51959-6
- Citations
- 6
- Primary Topic
- vaccines and immunoinformatics approaches
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- National Psoriasis Foundation
- Innovationsfonden
- Rebecca L. Cooper Medical Research Foundation
- Monash University
- Medical Research Council
- National Health and Medical Research Council