TY - JOUR
T1 - Screening of Oncogenic Proteins and Development of a Multiepitope Peptide Vaccine Targeting AKT1 and PARP1 for Breast Cancer by Integrating Reverse Vaccinology and Immune-Informatics Approaches
AU - Gupta, Sakshi
AU - Desai, Drishti
AU - Patel, Manasi
AU - Jyotishi, Charmi
AU - Saleh, Ahmad Mahmoud
AU - Gupta, Reeshu
N1 - Publisher Copyright:
© (2025), (Asian Pacific Organization for Cancer Prevention). All rights reserved.
PY - 2025
Y1 - 2025
N2 - Background: Breast cancer remains a significant global health challenge, requiring innovative therapeutic strategies. In silico methods, which leverage computational tools, offer a promising pathway for vaccine development. These methods facilitate antigen identification, epitope prediction, immune response modelling, and vaccine optimization, accelerating the design process. Methods: This study employed a reverse vaccinology approach combined with various bioinformatic tools to design a multi-epitope peptide vaccine. Results: Using reverse vaccinology, AKT1 and PARP1 were identified as potential vaccine candidates, as their expression levels were significantly higher in breast cancer samples compared to healthy controls. The vaccine was designed by integrating immune cell epitopes with a TLR4 agonist as an adjuvant. It demonstrated high antigenicity, no allergenicity, and no toxicity. Validation of its 3D structure using the Ramachandran plot confirmed optimal conformation and stereochemical properties. Molecular docking and simulation studies showed the vaccine was stable and compact when interacting with TLR4. Moreover, the subunit vaccine effectively eliminated the antigen and triggered a strong IgG/IgM immune response lasting approximately one year (350 days). Conclusion: These findings suggest that the designed vaccine holds promise as a therapeutic option for breast cancer. However, further in vitro and in vivo studies are necessary to validate its efficacy before advancing to clinical trials.
AB - Background: Breast cancer remains a significant global health challenge, requiring innovative therapeutic strategies. In silico methods, which leverage computational tools, offer a promising pathway for vaccine development. These methods facilitate antigen identification, epitope prediction, immune response modelling, and vaccine optimization, accelerating the design process. Methods: This study employed a reverse vaccinology approach combined with various bioinformatic tools to design a multi-epitope peptide vaccine. Results: Using reverse vaccinology, AKT1 and PARP1 were identified as potential vaccine candidates, as their expression levels were significantly higher in breast cancer samples compared to healthy controls. The vaccine was designed by integrating immune cell epitopes with a TLR4 agonist as an adjuvant. It demonstrated high antigenicity, no allergenicity, and no toxicity. Validation of its 3D structure using the Ramachandran plot confirmed optimal conformation and stereochemical properties. Molecular docking and simulation studies showed the vaccine was stable and compact when interacting with TLR4. Moreover, the subunit vaccine effectively eliminated the antigen and triggered a strong IgG/IgM immune response lasting approximately one year (350 days). Conclusion: These findings suggest that the designed vaccine holds promise as a therapeutic option for breast cancer. However, further in vitro and in vivo studies are necessary to validate its efficacy before advancing to clinical trials.
KW - Breast cancer
KW - Immunoinformatics
KW - Reverse vaccinology
KW - TLR4
UR - https://www.scopus.com/pages/publications/85217091364
U2 - 10.31557/APJCP.2025.26.1.327
DO - 10.31557/APJCP.2025.26.1.327
M3 - Article
C2 - 39874016
AN - SCOPUS:85217091364
SN - 1513-7368
VL - 26
SP - 327
EP - 338
JO - Asian Pacific Journal of Cancer Prevention
JF - Asian Pacific Journal of Cancer Prevention
IS - 1
ER -