iScience (Jun 2023)
Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations
- Camilla Tiezzi,
- Andrea Vecchi,
- Marzia Rossi,
- Davide Cavazzini,
- Angelo Bolchi,
- Diletta Laccabue,
- Sara Doselli,
- Amalia Penna,
- Luca Sacchelli,
- Federica Brillo,
- Tiziana Meschi,
- Andrea Ticinesi,
- Antonio Nouvenne,
- Gaetano Donofrio,
- Paola Zanelli,
- Magda Benecchi,
- Silvia Giuliodori,
- Paola Fisicaro,
- Ilaria Montali,
- Camilla Ceccatelli Berti,
- Valentina Reverberi,
- Anna Montali,
- Simona Urbani,
- Giuseppe Pedrazzi,
- Gabriele Missale,
- Amalio Telenti,
- Davide Corti,
- Simone Ottonello,
- Carlo Ferrari,
- Carolina Boni
Affiliations
- Camilla Tiezzi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Andrea Vecchi
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Marzia Rossi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Davide Cavazzini
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Angelo Bolchi
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; Interdepartmental Center Biopharmanet-Tec, University of Parma, Parma, Italy
- Diletta Laccabue
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Sara Doselli
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Amalia Penna
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Luca Sacchelli
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Federica Brillo
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Tiziana Meschi
- Department of Medicine and Surgery, University of Parma, Parma, Italy; Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Andrea Ticinesi
- Department of Medicine and Surgery, University of Parma, Parma, Italy; Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Antonio Nouvenne
- Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Gaetano Donofrio
- Department of Veterinary Science, University of Parma, Parma, Italy
- Paola Zanelli
- Unità di Immunogenetica dei Trapianti, Azienda Ospedaliero Universitaria di Parma, Parma, Italy
- Magda Benecchi
- Unità di Immunogenetica dei Trapianti, Azienda Ospedaliero Universitaria di Parma, Parma, Italy
- Silvia Giuliodori
- Unità di Immunogenetica dei Trapianti, Azienda Ospedaliero Universitaria di Parma, Parma, Italy
- Paola Fisicaro
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Ilaria Montali
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Camilla Ceccatelli Berti
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Valentina Reverberi
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Anna Montali
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Simona Urbani
- UO Immunoematologia e Medicina Trasfusionale, Dipartimento Diagnostico, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- Giuseppe Pedrazzi
- Department of Neuroscience - Biophysics and Medical Physics Unit, University of Parma, Parma, Italy
- Gabriele Missale
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy
- Amalio Telenti
- Vir Biotechnology, San Francisco, CA 94158, USA
- Davide Corti
- Humabs Biomed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland
- Simone Ottonello
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; Interdepartmental Center Biopharmanet-Tec, University of Parma, Parma, Italy
- Carlo Ferrari
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy; Corresponding author
- Carolina Boni
- Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Corresponding author
- Journal volume & issue
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Vol. 26,
no. 6
p. 106940
Abstract
Summary: Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but CD8 T cells seem to be more resistant to mutational inactivation. By a systematic analysis of 30 spike variant peptides containing the most relevant VOC and VOI mutations that have accumulated overtime, we show that in vaccinated and convalescent subjects, mutated epitopes can have not only a neutral or inhibitory effect on CD8 T cell recognition but can also enhance or generate de novo CD8 T cell responses. The emergence of these mutated T cell function enhancing epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased virus transmissibility. In a subset of individuals with weak and narrowly focused CD8 T cell responses selection of these heteroclitic-like epitopes may bear clinical relevance by improving antiviral protection. The functional enhancing effect of these peptides is also worth of consideration for the future development of new generation, more potent COVID-19 vaccines.
