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Int J Biol Macromol . PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines

tetano

Editor, Senior Moderator
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[SUP] 1 [/SUP], Jacopo Chiaro[SUP] 1 [/SUP], Manlio Fusciello[SUP] 1 [/SUP], Salvatore Russo[SUP] 1 [/SUP], Iivari Kleino[SUP] 2 [/SUP], Leena Ylösmäki[SUP] 3 [/SUP], Eliisa Kekäläinen[SUP] 4 [/SUP], Johanna Hastbacka[SUP] 5 [/SUP], Pirkka T Pekkarinen[SUP] 6 [/SUP], Erkko Ylösmäki[SUP] 1 [/SUP], Stefania Capone[SUP] 7 [/SUP], Antonella Folgori[SUP] 7 [/SUP], Angelo Raggioli[SUP] 7 [/SUP], Carolina Boni[SUP] 8 [/SUP], Camilla Tezzi[SUP] 9 [/SUP], Andrea Vecchi[SUP] 8 [/SUP], Monica Gelzo[SUP] 10 [/SUP], Hassen Kared[SUP] 11 [/SUP], Alessandra Nardin[SUP] 11 [/SUP], Michael Fehlings[SUP] 11 [/SUP], Veronique Barban[SUP] 3 [/SUP], Petra Ahokas[SUP] 3 [/SUP], Tapani Viitala[SUP] 12 [/SUP], Giuseppe Castaldo[SUP] 10 [/SUP], Lucio Pastore[SUP] 13 [/SUP], Paul Porter[SUP] 14 [/SUP], Sari Pesonen[SUP] 3 [/SUP], Vincenzo Cerullo[SUP] 15 [/SUP]



Affiliations
Abstract

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.

 
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