Novel HER2-based multi-epitope vaccine (HER2-MEV) against HER2-positive breast cancer: In silico design and validation

Abstract

Breast cancer (BC) continues to be the malignancy with the highest diagnosis rate worldwide. Between 15 % and 30 % of BC patients show overexpressed human epidermal growth factor receptor 2 (HER2), which is linked to poor clinical results in terms of invasiveness and recurrence risk. Passive immunity-based therapeutic approaches for treating HER2-enriched BC, are not effective and significant problems need to be tackled. Constructing multi-epitope vaccines is favored over single-epitope vaccines due to its ability to induce immunity against a variety of antigenic targets which will improve the efficacy of the vaccine. The current study describes a multi-epitope vaccine from HER2 protein against HER2-positive BC using several immunoinformatic techniques to achieve a potent and durable immune response. Nine Cytotoxic T lymphocytes (CTL) and five Helper T lymphocytes (HTL) epitopes were predicted and validated from HER2 protein using in silico tools. The expressed protein of the designed vaccine is predicted to be highly thermostable with better solubility. The predicted vaccine 3D structure was validated by ProSA servers and by the ERRAT server. Molecular docking analysis revealed a high binding affinity and stability of the designed vaccine with MHCI and TLR-2, 4, 7, and 9 receptors. The analysis of the C-ImmSim server revealed that the novel vaccine construct had the ability to elicit robust anti-cancerous innate, humoral, and cell-mediated immune responses. The vaccine can be a suitable option for HER2-positive BC patients and other patients with HER2-positive cancers to evoke immune responses. However, in vitro and in vivo experiments are needed to assess its effectiveness and safety.