Development of multi-epitope vaccine constructs for non-small cell lung cancer (NSCLC) against USA human leukocyte antigen background: an immunoinformatic approach toward future vaccine designing
Sana Batool, Duaa Bin-T-Abid, Hina Batool, Saher Shahid, Mahjabeen Saleem, Azmat Ullah, Arslan Hamid, Malik Siddique Mahmood, Naeem Mahmood Ashraf
Abstract
Objectives The design of peptide-based vaccines for cancer is a promising immunotherapy that can induce a cancer-specific cytotoxic response in tumor cells.Methods Herein, we used the immunoinformatic approach in designing a multi-epitope vaccine targeting G-protein coupled receptor 87 (GPCR-87), cystine/glutamate transporter (SLC7A11), Immunoglobulin binding protein 1 (IGBP1), and thioredoxin domain-containing protein 5 (TXNDC5), which can potentially contribute to NSCLC. The MHC-I and MHC-II epitopes selected for the fusion construct were evaluated for their antigenic and non-allergenic natures via VaxiJen and AllerTop.Results A total of five epitopes, four class-I (FIFYLKNIV, CRYTSVLFY, RYLKVVKPF, and RQAKIQRYK), and one class-II (NQVRGYPTLLWFRDG), having combined USA population coverage of 100%, were used to make ten possible multi-epitope fusion constructs. In these constructs, PADRE, a universal T-helper epitope, and RSO9, a TLR4 agonist, were fused as adjuvants. The molecular docking analysis revealed that two constructs were showing significant binding affinities toward HLA-A*02:01, the most prevalent HLA allele in USA. Moreover, MD simulations marked one construct as a promising therapeutic candidate.Conclusion The multi-epitope vaccine constructs designed using immunogenic, and non-allergenic peptides of NSCLS tumor-associated proteins are likely to pose significant therapeutic efficacies in cancer immunotherapy due to their high binding affinities toward HLA molecules.