Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design

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 melanom...

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Main Authors: Iker Malaina, Lorena Gonzalez-Melero, Luis Martínez, Aiala Salvador, Ana Sanchez-Diez, Aintzane Asumendi, Javier Margareto, Jose Carrasco-Pujante, Leire Legarreta, María Asunción García, Martín Blas Pérez-Pinilla, Rosa Izu, Ildefonso Martínez de la Fuente, Manoli Igartua, Santos Alonso, Rosa Maria Hernandez, María Dolores Boyano
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/10/9024
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author Iker Malaina
Lorena Gonzalez-Melero
Luis Martínez
Aiala Salvador
Ana Sanchez-Diez
Aintzane Asumendi
Javier Margareto
Jose Carrasco-Pujante
Leire Legarreta
María Asunción García
Martín Blas Pérez-Pinilla
Rosa Izu
Ildefonso Martínez de la Fuente
Manoli Igartua
Santos Alonso
Rosa Maria Hernandez
María Dolores Boyano
author_facet Iker Malaina
Lorena Gonzalez-Melero
Luis Martínez
Aiala Salvador
Ana Sanchez-Diez
Aintzane Asumendi
Javier Margareto
Jose Carrasco-Pujante
Leire Legarreta
María Asunción García
Martín Blas Pérez-Pinilla
Rosa Izu
Ildefonso Martínez de la Fuente
Manoli Igartua
Santos Alonso
Rosa Maria Hernandez
María Dolores Boyano
author_sort Iker Malaina
collection DOAJ
description 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 (<i>p</i>-value 0.03). However, neither HLA-I binding affinity (<i>p</i>-value 0.08) nor Class I immunogenicity values (<i>p</i>-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.
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spelling doaj.art-9eda8a8c420d4e0ca9ec9566ae3f8edd2023-11-18T01:46:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410902410.3390/ijms24109024Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine DesignIker Malaina0Lorena Gonzalez-Melero1Luis Martínez2Aiala Salvador3Ana Sanchez-Diez4Aintzane Asumendi5Javier Margareto6Jose Carrasco-Pujante7Leire Legarreta8María Asunción García9Martín Blas Pérez-Pinilla10Rosa Izu11Ildefonso Martínez de la Fuente12Manoli Igartua13Santos Alonso14Rosa Maria Hernandez15María Dolores Boyano16Department of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Dermatology, Basurto University Hospital, 48013 Bilbao, SpainBiocruces Bizkaia Health Research Institute, 48903 Barakaldo, SpainTechnological Services Division, Health and Quality of Life, TECNALIA, 01510 Miñano, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Dermatology, Basurto University Hospital, 48013 Bilbao, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainBiocruces Bizkaia Health Research Institute, 48903 Barakaldo, SpainIn 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 (<i>p</i>-value 0.03). However, neither HLA-I binding affinity (<i>p</i>-value 0.08) nor Class I immunogenicity values (<i>p</i>-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.https://www.mdpi.com/1422-0067/24/10/9024bioinformaticsex vivohuman leucocytic antigenimmunogenicitynanoparticleneoantigen
spellingShingle Iker Malaina
Lorena Gonzalez-Melero
Luis Martínez
Aiala Salvador
Ana Sanchez-Diez
Aintzane Asumendi
Javier Margareto
Jose Carrasco-Pujante
Leire Legarreta
María Asunción García
Martín Blas Pérez-Pinilla
Rosa Izu
Ildefonso Martínez de la Fuente
Manoli Igartua
Santos Alonso
Rosa Maria Hernandez
María Dolores Boyano
Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
International Journal of Molecular Sciences
bioinformatics
ex vivo
human leucocytic antigen
immunogenicity
nanoparticle
neoantigen
title Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
title_full Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
title_fullStr Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
title_full_unstemmed Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
title_short Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
title_sort computational and experimental evaluation of the immune response of neoantigens for personalized vaccine design
topic bioinformatics
ex vivo
human leucocytic antigen
immunogenicity
nanoparticle
neoantigen
url https://www.mdpi.com/1422-0067/24/10/9024
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