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Background <p>Gastrointestinal adenocarcinomas are a major cause of mortality globally, underpinning the desire for new approaches to immunotherapeutic strategies. SEPT9 is clinically validated as an FDA-approved colorectal cancer biomarker, suggesting its potential as a candidate antigen for vaccine development.</p> Methods <p>An immunoinformatic pipeline created a multi-epitope chimera vaccination using strict standards of high antigenicity, non-allergenicity, non-toxicity, and worldwide population coverage. Five epitopes (three MHC-I and two MHC-II) were ranked from SEPT9. Selected epitopes were concatenated with suitable linkers for MHC-I and MHC-II, connected to a human β-defensin adjuvant. The construct composed of 134 amino acids was built using the trRosetta algorithm, refined using the GalaxyRefine2.0 algorithm, and validate via PROCHECK, ERRAT and ProSA. Immune response prediction was conducted by performing docking studies against TLR2 and TLR4 (via ClusPro software), and performing C-ImmSim immune simulations.</p> Results <p>The designed construct demonstrated predicted favorable physicochemical properties (solubility: 0.89), safety, and immunogenicity potential in silico. Docking ΔG values (TLR2: –17.7 kcal/mol; TLR4: –23.9 kcal/mol) and immune simulation data indicated theoretical potential to trigger innate and adaptive immunity.</p> Conclusion <p>The SEPT9-based multi-epitope vaccine construct demonstrated promising predicted immunogenic and structural properties in silico. However, these findings are computational and hypothesis-generating; experimental validation is required to assess immunogenicity, safety, and therapeutic efficacy in biological systems.</p>

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In silico design and immunoinformatics evaluation of a multi-epitope vaccine targeting SEPT9 for gastrointestinal adenocarcinomas

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月27日

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  • Harsh Kashyap,
  • Bhawna Rathi,
  • Harkirat Singh,
  • Navkiran Kaur,
  • Shivani Sharda,
  • Amarish Kumar Sharma

摘要

Background

Gastrointestinal adenocarcinomas are a major cause of mortality globally, underpinning the desire for new approaches to immunotherapeutic strategies. SEPT9 is clinically validated as an FDA-approved colorectal cancer biomarker, suggesting its potential as a candidate antigen for vaccine development.

Methods

An immunoinformatic pipeline created a multi-epitope chimera vaccination using strict standards of high antigenicity, non-allergenicity, non-toxicity, and worldwide population coverage. Five epitopes (three MHC-I and two MHC-II) were ranked from SEPT9. Selected epitopes were concatenated with suitable linkers for MHC-I and MHC-II, connected to a human β-defensin adjuvant. The construct composed of 134 amino acids was built using the trRosetta algorithm, refined using the GalaxyRefine2.0 algorithm, and validate via PROCHECK, ERRAT and ProSA. Immune response prediction was conducted by performing docking studies against TLR2 and TLR4 (via ClusPro software), and performing C-ImmSim immune simulations.

Results

The designed construct demonstrated predicted favorable physicochemical properties (solubility: 0.89), safety, and immunogenicity potential in silico. Docking ΔG values (TLR2: –17.7 kcal/mol; TLR4: –23.9 kcal/mol) and immune simulation data indicated theoretical potential to trigger innate and adaptive immunity.

Conclusion

The SEPT9-based multi-epitope vaccine construct demonstrated promising predicted immunogenic and structural properties in silico. However, these findings are computational and hypothesis-generating; experimental validation is required to assess immunogenicity, safety, and therapeutic efficacy in biological systems.