Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1
Abstract Tumor cells express programmed cell death ligand 1 (PD-L1), which recognizes the immune checkpoint molecule programmed cell death 1 (PD-1) on T cells, suppressing the antitumor immune response. Inhibiting the PD-1:PD-L1 interaction has the potential to reactivate the immune response against...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-87063-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184097935130624 |
|---|---|
| author | Syed Sahajada Mahafujul Alam Showkat Ahmad Mir Arijit Samanta Binata Nayak Safdar Ali Mehboob Hoque |
| author_facet | Syed Sahajada Mahafujul Alam Showkat Ahmad Mir Arijit Samanta Binata Nayak Safdar Ali Mehboob Hoque |
| author_sort | Syed Sahajada Mahafujul Alam |
| collection | DOAJ |
| description | Abstract Tumor cells express programmed cell death ligand 1 (PD-L1), which recognizes the immune checkpoint molecule programmed cell death 1 (PD-1) on T cells, suppressing the antitumor immune response. Inhibiting the PD-1:PD-L1 interaction has the potential to reactivate the immune response against tumors. Recent advancements in cancer therapy have demonstrated remarkable promise of immunotherapy, which exploits immune checkpoint inhibition by small molecules or monoclonal antibodies. This strategy has shown impressive clinical success in treating a wide range of cancer subtypes, albeit with certain limitations. This study aims to design a novel multi-epitope vaccine against PD-L1 by using an immunoinformatics approach. For attaining enhanced efficacy and minimize side effects, the vaccine was constructed using antigenic, non-allergenic, and non-toxic epitopes (5 CTL, 3 HTL, and 2 B-cell epitopes) predicted from the IgV domain of PD-L1. The vaccine design includes a large ribosomal subunit protein bL12 adjuvant, a 6xHis tag for purification, and appropriate linkers to connect the epitopes. The modelled 3D structure of the vaccine construct was docked with TLR4 immune receptor, demonstrating strong antigenic properties and stable binding, as validated by molecular dynamics simulations. Immune simulation studies suggest that the vaccine construct could potentially elicit significant immune regulators such as B cells, T-cells, and memory cells. Thus, the findings indicate that the vaccine may effectively suppress the PD-1:PD-L1 axis by targeting PD-L1, restoring the anticancer immune response. However, its efficacy needs to be validated in both in vitro and in vivo settings. |
| format | Article |
| id | doaj-art-6e50f74d19b94e68ae71c78695d4a68f |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6e50f74d19b94e68ae71c78695d4a68f2025-08-20T02:17:09ZengNature PortfolioScientific Reports2045-23222025-04-0115112610.1038/s41598-025-87063-yImmunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1Syed Sahajada Mahafujul Alam0Showkat Ahmad Mir1Arijit Samanta2Binata Nayak3Safdar Ali4Mehboob Hoque5Applied Biochemistry Laboratory, Department of Biological Sciences, Aliah UniversitySchool of Life Sciences, Sambalpur UniversityApplied Biochemistry Laboratory, Department of Biological Sciences, Aliah UniversitySchool of Life Sciences, Sambalpur UniversityClinical and Applied Genomics (CAG) Laboratory, Department of Biological Sciences, Aliah UniversityApplied Biochemistry Laboratory, Department of Biological Sciences, Aliah UniversityAbstract Tumor cells express programmed cell death ligand 1 (PD-L1), which recognizes the immune checkpoint molecule programmed cell death 1 (PD-1) on T cells, suppressing the antitumor immune response. Inhibiting the PD-1:PD-L1 interaction has the potential to reactivate the immune response against tumors. Recent advancements in cancer therapy have demonstrated remarkable promise of immunotherapy, which exploits immune checkpoint inhibition by small molecules or monoclonal antibodies. This strategy has shown impressive clinical success in treating a wide range of cancer subtypes, albeit with certain limitations. This study aims to design a novel multi-epitope vaccine against PD-L1 by using an immunoinformatics approach. For attaining enhanced efficacy and minimize side effects, the vaccine was constructed using antigenic, non-allergenic, and non-toxic epitopes (5 CTL, 3 HTL, and 2 B-cell epitopes) predicted from the IgV domain of PD-L1. The vaccine design includes a large ribosomal subunit protein bL12 adjuvant, a 6xHis tag for purification, and appropriate linkers to connect the epitopes. The modelled 3D structure of the vaccine construct was docked with TLR4 immune receptor, demonstrating strong antigenic properties and stable binding, as validated by molecular dynamics simulations. Immune simulation studies suggest that the vaccine construct could potentially elicit significant immune regulators such as B cells, T-cells, and memory cells. Thus, the findings indicate that the vaccine may effectively suppress the PD-1:PD-L1 axis by targeting PD-L1, restoring the anticancer immune response. However, its efficacy needs to be validated in both in vitro and in vivo settings.https://doi.org/10.1038/s41598-025-87063-yCancer immunotherapyCancer vaccineImmunoinformaticsMulti-epitope vaccinePD-L1 |
| spellingShingle | Syed Sahajada Mahafujul Alam Showkat Ahmad Mir Arijit Samanta Binata Nayak Safdar Ali Mehboob Hoque Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 Scientific Reports Cancer immunotherapy Cancer vaccine Immunoinformatics Multi-epitope vaccine PD-L1 |
| title | Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 |
| title_full | Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 |
| title_fullStr | Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 |
| title_full_unstemmed | Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 |
| title_short | Immunoinformatics based designing of a multi-epitope cancer vaccine targeting programmed cell death ligand 1 |
| title_sort | immunoinformatics based designing of a multi epitope cancer vaccine targeting programmed cell death ligand 1 |
| topic | Cancer immunotherapy Cancer vaccine Immunoinformatics Multi-epitope vaccine PD-L1 |
| url | https://doi.org/10.1038/s41598-025-87063-y |
| work_keys_str_mv | AT syedsahajadamahafujulalam immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 AT showkatahmadmir immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 AT arijitsamanta immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 AT binatanayak immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 AT safdarali immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 AT mehboobhoque immunoinformaticsbaseddesigningofamultiepitopecancervaccinetargetingprogrammedcelldeathligand1 |