Mapping the immunopeptidome of seven SARS-CoV-2 antigens across common HLA haplotypes

Asolina Braun, Louise C. Rowntree, Ziyi Huang, Kirti Pandey, Nikolas Thuesen, Chen Li, Jan Petersen, Dene R. Littler, Shabana Raji, Thi H. O. Nguyen, Emma Jappe Lange, Gry Persson, Michael Schantz Klausen, Jens Kringelum, Shanzou Chung, Nathan P. Croft, Pouya Faridi, Rochelle Ayala, Jamie Rossjohn, Patricia T. Illing, Katherine E. Scull, Sri Ramarathinam, Nicole A. Mifsud, Katherine Kedzierska, Anders Bundgård Sørensen and Anthony W. Purcell ()
Additional contact information
Asolina Braun: Monash University
Louise C. Rowntree: at the Peter Doherty Institute for Infection and Immunity
Ziyi Huang: Monash University
Kirti Pandey: Monash University
Nikolas Thuesen: Evaxion Biotech
Chen Li: Monash University
Jan Petersen: Monash University
Dene R. Littler: Monash University
Shabana Raji: at the Peter Doherty Institute for Infection and Immunity
Thi H. O. Nguyen: at the Peter Doherty Institute for Infection and Immunity
Emma Jappe Lange: Evaxion Biotech
Gry Persson: Evaxion Biotech
Michael Schantz Klausen: Evaxion Biotech
Jens Kringelum: Evaxion Biotech
Shanzou Chung: Monash University
Nathan P. Croft: Monash University
Pouya Faridi: Monash University
Rochelle Ayala: Monash University
Jamie Rossjohn: Monash University
Patricia T. Illing: Monash University
Katherine E. Scull: Monash University
Sri Ramarathinam: Monash University
Nicole A. Mifsud: Monash University
Katherine Kedzierska: at the Peter Doherty Institute for Infection and Immunity
Anders Bundgård Sørensen: Evaxion Biotech
Anthony W. Purcell: Monash University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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+ and CD4+ 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.

Date: 2024
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DOI: 10.1038/s41467-024-51959-6

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