tetano
Editor, Senior Moderator
Nat Commun
. 2024 Nov 28;15(1):10316.
doi: 10.1038/s41467-024-54734-9. Machine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines
Kevin A Kovalchik[SUP] #[/SUP][SUP] 1 [/SUP], David J Hamelin[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Peter Kubiniok[SUP] #[/SUP][SUP] 1 [/SUP], Benoîte Bourdin[SUP] 1 [/SUP], Fatima Mostefai[SUP] 2 3 4 [/SUP], Raphaël Poujol[SUP] 2 [/SUP], Bastien Paré[SUP] 1 [/SUP], Shawn M Simpson[SUP] 1 [/SUP], John Sidney[SUP] 5 [/SUP], Éric Bonneil[SUP] 6 [/SUP], Mathieu Courcelles[SUP] 6 [/SUP], Sunil Kumar Saini[SUP] 7 [/SUP], Mohammad Shahbazy[SUP] 8 [/SUP], Saketh Kapoor[SUP] 9 [/SUP], Vigneshwar Rajesh[SUP] 9 [/SUP], Maya Weitzen[SUP] 9 [/SUP], Jean-Christophe Grenier[SUP] 2 [/SUP], Bayrem Gharsallaoui[SUP] 1 [/SUP], Loïze Maréchal[SUP] 1 [/SUP], Zhaoguan Wu[SUP] 1 [/SUP], Christopher Savoie[SUP] 1 [/SUP], Alessandro Sette[SUP] 5 [/SUP], Pierre Thibault[SUP] 6 10 [/SUP], Isabelle Sirois[SUP] 1 [/SUP], Martin A Smith[SUP] 1 4 [/SUP], Hélène Decaluwe[SUP] 1 11 12 [/SUP], Julie G Hussin[SUP] 13 14 15 16 [/SUP], Mathieu Lavallée-Adam[SUP] 17 18 [/SUP], Etienne Caron[SUP] 19 20 21 [/SUP]
Affiliations
Next-generation T-cell-directed vaccines for COVID-19 focus on establishing lasting T-cell immunity against current and emerging SARS-CoV-2 variants. Precise identification of conserved T-cell epitopes is critical for designing effective vaccines. Here we introduce a comprehensive computational framework incorporating a machine learning algorithm-MHCvalidator-to enhance mass spectrometry-based immunopeptidomics sensitivity. MHCvalidator identifies unique T-cell epitopes presented by the B7 supertype, including an epitope from a + 1-frameshift in a truncated Spike antigen, supported by ribosome profiling. Analysis of 100,512 COVID-19 patient proteomes shows Spike antigen truncation in 0.85% of cases, revealing frameshifted viral antigens at the population level. Our EpiTrack pipeline tracks global mutations of MHCvalidator-identified CD8 + T-cell epitopes from the BNT162b4 vaccine. While most vaccine epitopes remain globally conserved, an immunodominant A*01-associated epitope mutates in Delta and Omicron variants. This work highlights SARS-CoV-2 antigenic features and emphasizes the importance of continuous adaptation in T-cell vaccine development.
. 2024 Nov 28;15(1):10316.
doi: 10.1038/s41467-024-54734-9. Machine learning-enhanced immunopeptidomics applied to T-cell epitope discovery for COVID-19 vaccines
Kevin A Kovalchik[SUP] #[/SUP][SUP] 1 [/SUP], David J Hamelin[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Peter Kubiniok[SUP] #[/SUP][SUP] 1 [/SUP], Benoîte Bourdin[SUP] 1 [/SUP], Fatima Mostefai[SUP] 2 3 4 [/SUP], Raphaël Poujol[SUP] 2 [/SUP], Bastien Paré[SUP] 1 [/SUP], Shawn M Simpson[SUP] 1 [/SUP], John Sidney[SUP] 5 [/SUP], Éric Bonneil[SUP] 6 [/SUP], Mathieu Courcelles[SUP] 6 [/SUP], Sunil Kumar Saini[SUP] 7 [/SUP], Mohammad Shahbazy[SUP] 8 [/SUP], Saketh Kapoor[SUP] 9 [/SUP], Vigneshwar Rajesh[SUP] 9 [/SUP], Maya Weitzen[SUP] 9 [/SUP], Jean-Christophe Grenier[SUP] 2 [/SUP], Bayrem Gharsallaoui[SUP] 1 [/SUP], Loïze Maréchal[SUP] 1 [/SUP], Zhaoguan Wu[SUP] 1 [/SUP], Christopher Savoie[SUP] 1 [/SUP], Alessandro Sette[SUP] 5 [/SUP], Pierre Thibault[SUP] 6 10 [/SUP], Isabelle Sirois[SUP] 1 [/SUP], Martin A Smith[SUP] 1 4 [/SUP], Hélène Decaluwe[SUP] 1 11 12 [/SUP], Julie G Hussin[SUP] 13 14 15 16 [/SUP], Mathieu Lavallée-Adam[SUP] 17 18 [/SUP], Etienne Caron[SUP] 19 20 21 [/SUP]
Affiliations
- PMID: 39609459
- PMCID: PMC11604954
- DOI: 10.1038/s41467-024-54734-9
Next-generation T-cell-directed vaccines for COVID-19 focus on establishing lasting T-cell immunity against current and emerging SARS-CoV-2 variants. Precise identification of conserved T-cell epitopes is critical for designing effective vaccines. Here we introduce a comprehensive computational framework incorporating a machine learning algorithm-MHCvalidator-to enhance mass spectrometry-based immunopeptidomics sensitivity. MHCvalidator identifies unique T-cell epitopes presented by the B7 supertype, including an epitope from a + 1-frameshift in a truncated Spike antigen, supported by ribosome profiling. Analysis of 100,512 COVID-19 patient proteomes shows Spike antigen truncation in 0.85% of cases, revealing frameshifted viral antigens at the population level. Our EpiTrack pipeline tracks global mutations of MHCvalidator-identified CD8 + T-cell epitopes from the BNT162b4 vaccine. While most vaccine epitopes remain globally conserved, an immunodominant A*01-associated epitope mutates in Delta and Omicron variants. This work highlights SARS-CoV-2 antigenic features and emphasizes the importance of continuous adaptation in T-cell vaccine development.