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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 10, p 9024 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms24109024
Popis: 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.
Databáze: Directory of Open Access Journals
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