Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
dc.contributor.author | Malaina Celada, Iker | |
dc.contributor.author | González Melero, Lorena | |
dc.contributor.author | Martínez Fernández, Luis | |
dc.contributor.author | Salvador Martínez, Aiala | |
dc.contributor.author | Sánchez Díez, Ana | |
dc.contributor.author | Asumendi Mallea, Aintzane | |
dc.contributor.author | Margareto, Javier | |
dc.contributor.author | Carrasco Pujante, José | |
dc.contributor.author | Legarreta Solaguren, Leire | |
dc.contributor.author | García, María Asunción | |
dc.contributor.author | Pérez Pinilla, Martín Blas | |
dc.contributor.author | Izu Belloso, Rosa María | |
dc.contributor.author | Martínez de la Fuente Martínez, Ildefonso Abel | |
dc.contributor.author | Igartua Olaechea, Manuela | |
dc.contributor.author | Alonso Alegre, Santos | |
dc.contributor.author | Hernández Martín, Rosa María | |
dc.contributor.author | Boyano López, María Dolores | |
dc.date.accessioned | 2023-08-09T11:55:28Z | |
dc.date.available | 2023-08-09T11:55:28Z | |
dc.date.issued | 2023-05-19 | |
dc.identifier.citation | International Journal of Molecular Sciences 24(10) : (2023) // Article ID 9024 | es_ES |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10810/62149 | |
dc.description.abstract | In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (p-value 0.03). However, neither HLA-I binding affinity (p-value 0.08) nor Class I immunogenicity values (p-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo. | es_ES |
dc.description.sponsorship | This work was supported by Basque Government funding (IT456-22; IT1448-22, IT693-22 and IT1524-22; ONKOVAC 2021111042), as well as by the UPV/EHU (GIU20/035; US21/27; US18/21; PIF18/295) and Basque Center of Applied Mathematics (US21/27 and US18/21). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | bioinformatics | es_ES |
dc.subject | ex vivo | es_ES |
dc.subject | human leucocytic antigen | es_ES |
dc.subject | immunogenicity | es_ES |
dc.subject | nanoparticle | es_ES |
dc.subject | neoantigen | es_ES |
dc.subject | vaccine design | es_ES |
dc.title | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2023-05-26T13:21:14Z | |
dc.rights.holder | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/1422-0067/24/10/9024 | es_ES |
dc.identifier.doi | 10.3390/ijms24109024 | |
dc.departamentoes | Dermatología, oftalmología y otorrinolaringología | |
dc.departamentoes | Biología celular e histología | |
dc.departamentoes | Matemáticas | |
dc.departamentoes | Farmacia y ciencias de los alimentos | |
dc.departamentoeu | Farmazia eta elikagaien zientziak | |
dc.departamentoeu | Matematika | |
dc.departamentoeu | Dermatologia, oftalmologia eta otorrinolaringologia | |
dc.departamentoeu | Zelulen biologia eta histologia |
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Except where otherwise noted, this item's license is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).