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Int J Biol Macromol
. 2024 Feb 6:129926.
doi: 10.1016/j.ijbiomac.2024.129926. Online ahead of print. PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines
Sara Feola 1 , Jacopo Chiaro 1 , Manlio Fusciello 1 , Salvatore Russo 1 , Iivari Kleino 2 , Leena Ylösmäki 3 , Eliisa Kekäläinen 4 , Johanna Hastbacka 5 , Pirkka T Pekkarinen 6 , Erkko Ylösmäki 1 , Stefania Capone 7 , Antonella Folgori 7 , Angelo Raggioli 7 , Carolina Boni 8 , Camilla Tezzi 9 , Andrea Vecchi 8 , Monica Gelzo 10 , Hassen Kared 11 , Alessandra Nardin 11 , Michael Fehlings 11 , Veronique Barban 3 , Petra Ahokas 3 , Tapani Viitala 12 , Giuseppe Castaldo 10 , Lucio Pastore 13 , Paul Porter 14 , Sari Pesonen 3 , Vincenzo Cerullo 15
Affiliations
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a threat to public health and the global economy, necessitating the development of various vaccination strategies. Mutations in the SPIKE protein gene, a crucial component of mRNA and adenovirus-based vaccines, raised concerns about vaccine efficacy, prompting the need for rapid vaccine updates. To address this, we leveraged PeptiCRAd, an oncolytic vaccine based on tumor antigen decorated oncolytic adenoviruses, creating a vaccine platform called PeptiVAX. First, we identified multiple CD8 T-cell epitopes from highly conserved regions across coronaviruses, expanding the range of T-cell responses to non-SPIKE proteins. We designed short segments containing the predicted epitopes presented by common HLA-Is in the global population. Testing the immunogenicity, we characterized T-cell responses to candidate peptides in peripheral blood mononuclear cells (PBMCs) from pre-pandemic healthy donors and ICU patients. As a proof of concept in mice, we selected a peptide with epitopes predicted to bind to murine MHC-I haplotypes. Our technology successfully elicited peptide-specific T-cell responses, unaffected by the use of unarmed adenoviral vectors or adeno-based vaccines encoding SPIKE. In conclusion, PeptiVAX represents a fast and adaptable SARS-CoV-2 vaccine delivery system that broadens T-cell responses beyond the SPIKE protein, offering potential benefits for vaccine effectiveness.
Keywords: PeptiVAX; Peptides; SARS-CoV-2; Viral platform.
. 2024 Feb 6:129926.
doi: 10.1016/j.ijbiomac.2024.129926. Online ahead of print. PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines
Sara Feola 1 , Jacopo Chiaro 1 , Manlio Fusciello 1 , Salvatore Russo 1 , Iivari Kleino 2 , Leena Ylösmäki 3 , Eliisa Kekäläinen 4 , Johanna Hastbacka 5 , Pirkka T Pekkarinen 6 , Erkko Ylösmäki 1 , Stefania Capone 7 , Antonella Folgori 7 , Angelo Raggioli 7 , Carolina Boni 8 , Camilla Tezzi 9 , Andrea Vecchi 8 , Monica Gelzo 10 , Hassen Kared 11 , Alessandra Nardin 11 , Michael Fehlings 11 , Veronique Barban 3 , Petra Ahokas 3 , Tapani Viitala 12 , Giuseppe Castaldo 10 , Lucio Pastore 13 , Paul Porter 14 , Sari Pesonen 3 , Vincenzo Cerullo 15
Affiliations
- PMID: 38331062
- DOI: 10.1016/j.ijbiomac.2024.129926
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a threat to public health and the global economy, necessitating the development of various vaccination strategies. Mutations in the SPIKE protein gene, a crucial component of mRNA and adenovirus-based vaccines, raised concerns about vaccine efficacy, prompting the need for rapid vaccine updates. To address this, we leveraged PeptiCRAd, an oncolytic vaccine based on tumor antigen decorated oncolytic adenoviruses, creating a vaccine platform called PeptiVAX. First, we identified multiple CD8 T-cell epitopes from highly conserved regions across coronaviruses, expanding the range of T-cell responses to non-SPIKE proteins. We designed short segments containing the predicted epitopes presented by common HLA-Is in the global population. Testing the immunogenicity, we characterized T-cell responses to candidate peptides in peripheral blood mononuclear cells (PBMCs) from pre-pandemic healthy donors and ICU patients. As a proof of concept in mice, we selected a peptide with epitopes predicted to bind to murine MHC-I haplotypes. Our technology successfully elicited peptide-specific T-cell responses, unaffected by the use of unarmed adenoviral vectors or adeno-based vaccines encoding SPIKE. In conclusion, PeptiVAX represents a fast and adaptable SARS-CoV-2 vaccine delivery system that broadens T-cell responses beyond the SPIKE protein, offering potential benefits for vaccine effectiveness.
Keywords: PeptiVAX; Peptides; SARS-CoV-2; Viral platform.