Details

Autor(en) / Beteiligte

• Malaina, Iker
• Gonzalez-Melero, Lorena
• Martínez, Luis
• Salvador, Aiala
• Sanchez-Diez, Ana
• Asumendi, Aintzane
• Margareto, Javier
• Carrasco-Pujante, Jose
• Legarreta, Leire
• García, María Asunción
• Pérez-Pinilla, Martín Blas
• Izu, Rosa
• Martínez de la Fuente, Ildefonso
• Igartua, Manoli
• Alonso, Santos
• Hernandez, Rosa Maria
• Boyano, María Dolores

Titel

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

Ist Teil von

• International journal of molecular sciences, 2023-05, Vol.24 (10), p.9024

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 ( -value 0.03). However, neither HLA-I binding affinity ( -value 0.08) nor Class I immunogenicity values ( -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.