Designing of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation
Md. Mijanur Rahman, Md. Habib Ullah Masum, Rehana Parvin, Shuvo Chandra Das, Asma Talukder
Abstract
Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins.
Introduction
Human papillomaviruses (HPVs) are small double-stranded DNA viruses belonging to the papillomaviridae family that cause infections in human mucous epithelia. It is the most frequent sexually transmitted disease (STD) worldwide [1]. HPV has been associated with 5% of cancer cases, affecting various parts of the human body, including the lung, cervix, penis, vulva, vagina, anus, and oropharynx, and thereby associated with cervical, penal, vulval, vaginal, anal, and oropharyngeal cancer [2–5]. Additionally, there is evidence suggesting the involvement of HPV in conjunctival malignancies [3].
Materials and method
Sequence retrieval
All available amino acid sequences of the E6 and E7 proteins of HPV 16 and HPV 18 were retrieved from the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm.nih.gov/) protein database in FASTA format [58]. The protein sequences were then aligned with MEGA X software to generate a consensus sequence. The consensus sequences of the proteins E6 and E7 were then applied for subsequent vaccine construction.
Results
Sequence retrieval
After obtaining the protein sequences E6 and E7 of HPV 16 and HPV 18 from the NCBI database, the multiple sequence analysis (MSA) analysis provided two consensus FASTA sequences of the proteins. These consensus sequences were then applied for the subsequent vaccine development. Fig 1 illustrates an empirical overview of the entire vaccine design process.
Discussion
Vaccination is a prerequisite for enhancing public health and boosting global well-being by protecting against HPV infection and its related health effects. There are six authorized HPV vaccines available, all of which are virus-like particles (VLPs) type vaccines, including three bivalent (Cervarix®, Cecolin®, and WalrinvaxV) [133–135], two quadrivalent (GARDASIL® and Cervavac®) [136, 137], and one ninevalent (GARDASIL9®) vaccine [138–140]. The bivalent vaccines provide protection against HPV types 16 and 18, which have been associated with over 70% of cervical cancers [141–143].
Conclusion
We successfully designed two mRNA vaccines targeting the E6 and E7 oncoproteins of the high-risk HPVs: HPV 16 and HPV 18. Bioinformatics tools aided epitope selection, with subsequent structural assessments confirming stability and antigenicity. Docking analysis revealed strong interactions between vaccines and TLRs, crucial for immune activation. Molecular dynamics simulations highlighted the stability and flexibility of vaccine complexes. Codon optimization ensured efficient expression in E. coli vectors.
Citation: Rahman MM, Masum MHU, Parvin R, Das SC, Talukder A (2025) Designing of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation. PLoS ONE 20(1): e0313559. https://doi.org/10.1371/journal.pone.0313559
Editor: Abu Tayab Moin, University of Chittagong, BANGLADESH
Received: August 12, 2024; Accepted: October 25, 2024; Published: January 6, 2025
Copyright: © 2025 Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
