Computational formulation of a multiepitope vaccine unveils an exceptional prophylactic candidate against Merkel cell polyomavirus

Abstract

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%–100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the in silico cloning of the vaccine into the pET28+(a) cloning vector. In conclusion, the vaccine candidate developed in this study is anticipated to augment the immune response in humans and effectively combat the virus. Nevertheless, it is imperative to conduct in vitro and in vivo assays to evaluate the efficacy of these vaccine candidates thoroughly. These evaluations will provide critical insights into the vaccine’s effectiveness and potential for further development.

Current Progress in Vaccines against Merkel Cell Carcinoma: A Narrative Review and Update

“…Given the general success of immunotherapy in MCC and the expression of a necessary viral protein shared by virus-positive cases, this tumor is a prime candidate for vaccination strategies. Consequently, the development of virus-directed vaccines against MCC has significantly increased in recent years [7,[43][44][45][46][47][48][49][50][51]. For example, peptide-and DNA-based vaccines and combination therapies with vaccines and ICI are currently being investigated for treatment of MCC in preclinical and clinical trials.…”

“…On PubMed Central, we identified 10 published papers on preclinical and clinical studies dealing with vaccine strategies against MCC, which have been summarized in Table 1 [7,8,[44][45][46][47][48][49][50][51]55]. Almost all studies summarized in Table 1 are of preclinical nature, including murine models and multiepitope computational vaccine design strategies; only three investigations had a phase I or II study design.…”

“…An in silico peptide design study also focused on the capsid proteins VP1 and VP2, since they were identified as best candidates [48,51]. The designed vaccine should be widely applicable and induce a good immune response.…”

“…For prophylactic vaccination, the disease is too rare to be cost-effective. Nevertheless, another in silico study designed a multiepitope vaccine for prophylactic vaccination [48]. Since the multiepitope vaccine also contained epitopes of sT and LT, this design could be at least partially tested as a therapeutic vaccine.…”

“…Since the multiepitope vaccine also contained epitopes of sT and LT, this design could be at least partially tested as a therapeutic vaccine. An in silico peptide design study also focused on the capsid proteins VP1 and VP2, since they were identified as best candidates [48,51]. The designed vaccine should be widely applicable and induce a good immune response.…”