In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4+ and CD8+ T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.

Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis

“…Since now we know enough information about SARS-CoV-2's genomics and proteomics, we can design peptide vaccines based on a neutralizing epitope. These immunoinformatics methods have made a significant impact on the immunology researches and we can see many examples of in silico design of epitope-based vaccines against many viruses including human immunodeficiency virus (HIV) [16], human papillomavirus (HPV) [38,39], SARS-CoV [40], rhinovirus [41]. SARS-CoV-2 is an RNA virus tending to mutate more frequently [42].…”

Clostridioides Difficile Toxin B (tcdB) Peptide Mimotope Antibody-capture Enzyme Immunoassay in the Detection of Colorectal Cancer

“…The epitope mapping tools used in this study have previously been used to identify immunogenic sequences of known antigens from infectious agents and cancer biomarkers [23,24]. Its applications ranged from vaccine research to diagnostic tool development, from which the outcomes for the latter is improvement in the sensitivity, specificity, or both in detection of diseases [25][26].…”

RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates

“…L1-VLPs have shown to be immunogenic and able to induce high-titers of protective neutralizing antibodies (nAb), which are triggered by repetitive and tightly spaced epitopes that readily activate B cells via the B cell receptor or toll-like receptor cross-linking. Additionally, L1 is rich in T cell epitopes needed to provide B cell help [ 35 , 36 , 37 ].…”