Exploring the Papillomaviral Proteome to Identify Potential Candidates for a Chimeric Vaccine against Cervix Papilloma Using Immunomics and Computational Structural Vaccinology

Abstract

The human papillomavirus (HPV) 58 is considered to be the second most predominant genotype in cervical cancer incidents in China. HPV type-restriction, non-targeted delivery, and the highcost of existing vaccines necessitate continuing research on the HPV vaccine. We aimed to explore the papillomaviral proteome in order to identify potential candidates for a chimeric vaccine against cervix papilloma using computational immunology and structural vaccinology approaches. Two overlapped epitope segments (23–36) and (29–42) from the N-terminal region of the HPV58 minor capsid protein L2 are selected as capable of inducing both cellular and humoral immunity. In total, 318 amino acid lengths of the vaccine construct SGD58 contain adjuvants (Flagellin and RS09), two Th epitopes, and linkers. SGD58 is a stable protein that is soluble, antigenic, and non-allergenic. Homology modeling and the structural refinement of the best models of SGD58 and TLR5 found 96.8% and 93.9% favored regions in Rampage, respectively. The docking results demonstrated a HADDOCK score of −62.5 ± 7.6, the binding energy (−30 kcal/mol) and 44 interacting amino acid residues between SGD58-TLR5 complex. The docked complex are stable in 100 ns of simulation. The coding sequences of SGD58 also show elevated gene expression in Escherichia coli with 1.0 codon adaptation index and 59.92% glycine-cysteine content. We conclude that SGD58 may prompt the creation a vaccine against cervix papilloma.

Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus

“…Refs. [67][68][69][70][71][72]) Such progress provides many additional tools and strategies that could be used. In some cases, one might find that repurposing existing drugs or herbal extracts with suspected genuine efficacy may help in the challenge.…”

COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance

“…A number of ideas and principles, borrowed in established and recent design of synthetic vaccines and petidomimetics, were used (see ref [3] for discussion and e.g. refs [63][64][65][66][67][68][69]), as well as some of the ideas that lie behind the popular ZINC data base [70]. As discussed in refs [3,4], the present investigation started as a use case for the Hyperbolic Dirac Net (HDN) and particularly the associated Q-UEL language for automated inference [34][35][36][37].…”

Immunomics Datasets and Tools: To Identify Potential Epitope Segments for Designing Chimeric Vaccine Candidate to Cervix Papilloma

“…GROMACS 5.1.2 package with CHARMM force field was used to perform MD simulation. The details of MD simulation illustrated in our previous study [36]. EMBOSS Backtranseq v1.0 [70] is a suitable tool to uptake the query protein sequences, reverse translated and returned the optimizing coding sequences.…”

“…The GenScript rare codon analysis [71] is a prominent tool for codon usage and its distribution analysis (codon adaptation index-CAI, glycine-cystine (GC) content, and codon frequency distribution (CFD) in the individual expression host organism based on the Optimum GeneTM algorithm. The details of virtual gene expression and cloning illustrated in our previous study [36]. All the supporting information deposited in Zenodo database [72].…”

“…Moreover, the virtual cloning and gene expression of the chimeric vaccine in E. coli were analyzed to obtain a low-cost HPV vaccine. All the necessary supporting information for SGD58 design illustrated in the study and the original results was reported in our previous study [36].…”