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<p><i>Toxoplasma gondii</i> infects approximately 30% of the population, and there is currently no approved vaccine. Identifying immunogenic peptides with high affinity to different HLA molecules is a promising vaccine strategy. This study used an in silico approach using artificial neural networks to identify <i>T. gondii</i> peptides restricted to HLA-A*02, HLA-A*24, and HLA-B*35 alleles. Proteomes from seven <i>T. gondii</i> strains and transcriptomic data of overexpressed genes from <i>T. gondii-</i>RH in human PBMC were also used. Parasite protein sequences were analyzed with R <i>‘Epitope Prediction’</i> library. Peptide candidates were evaluated in the artificial neural networks based on the probabilities of output neurons (<i>p</i> &gt; 0.5). The IFN-γ responses in PBMC from <i>T. gondii</i> seronegative and seropositive individuals were evaluated by ELISpot. Peptides with higher IFN-γ induction were evaluated to identify cytotoxic response in CD8<sup>+</sup> T cells (CD107a). In silico analysis identified 36 peptides from <i>T. gondii</i> proteins with predicted affinity to HLA-A*02, A*24, and B*35 alleles. Experiments with PBMCs revealed that a peptide restricted to HLA-A02 (P1: FLFAWITYV) induced a significant increase in IFN-γ-producing cells (<i>p</i> = 0.004). For HLA-A24, a peptide (P8: VFAFAFAFFLI) also induced a significant IFN-γ response (<i>p</i> = 0.004), while for the HLA-B*35 allele, the P6 peptide (YPIAPSFAM) induced a response that differed significantly from the control (<i>p</i> = 0.05). These peptides induced also a significant percentage of central memory CD8 + T cells expressing the degranulation marker CD107a (<i>p</i> &lt; 0.05). Finally, we identified three <i>T. gondii</i> peptides that induced IFN-γ response, and a cytotoxic response measured by CD107a expression on CD45RAneg-CD8 cells. These peptides could be considered part of a multi-epitope vaccine against toxoplasmosis in humans.</p>

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In silico identification and ex vivo evaluation of Toxoplasma gondii peptides restricted to HLA-A*02, HLA-A*24 and HLA-B*35 alleles in human PBMC from a Colombian population

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  • 发表日期：

    2024年12月31日

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  • Mónica Vargas-Montes,
  • María Camila Valencia-Jaramillo,
  • Juan David Valencia-Hernández,
  • Jorge Enrique Gómez-Marín,
  • Ailan Farid Arenas,
  • Néstor Cardona

摘要

Toxoplasma gondii infects approximately 30% of the population, and there is currently no approved vaccine. Identifying immunogenic peptides with high affinity to different HLA molecules is a promising vaccine strategy. This study used an in silico approach using artificial neural networks to identify T. gondii peptides restricted to HLA-A*02, HLA-A*24, and HLA-B*35 alleles. Proteomes from seven T. gondii strains and transcriptomic data of overexpressed genes from T. gondii-RH in human PBMC were also used. Parasite protein sequences were analyzed with R ‘Epitope Prediction’ library. Peptide candidates were evaluated in the artificial neural networks based on the probabilities of output neurons (p > 0.5). The IFN-γ responses in PBMC from T. gondii seronegative and seropositive individuals were evaluated by ELISpot. Peptides with higher IFN-γ induction were evaluated to identify cytotoxic response in CD8+ T cells (CD107a). In silico analysis identified 36 peptides from T. gondii proteins with predicted affinity to HLA-A*02, A*24, and B*35 alleles. Experiments with PBMCs revealed that a peptide restricted to HLA-A02 (P1: FLFAWITYV) induced a significant increase in IFN-γ-producing cells (p = 0.004). For HLA-A24, a peptide (P8: VFAFAFAFFLI) also induced a significant IFN-γ response (p = 0.004), while for the HLA-B*35 allele, the P6 peptide (YPIAPSFAM) induced a response that differed significantly from the control (p = 0.05). These peptides induced also a significant percentage of central memory CD8 + T cells expressing the degranulation marker CD107a (p < 0.05). Finally, we identified three T. gondii peptides that induced IFN-γ response, and a cytotoxic response measured by CD107a expression on CD45RAneg-CD8 cells. These peptides could be considered part of a multi-epitope vaccine against toxoplasmosis in humans.