Combination of human papillomaviruses L1 and L2 multiepitope constructs protects mice against tumor cells. (16th June 2021)

• Record Type: Journal Article
• Authors: Namvar, Ali; Bolhassani, Azam; Javadi, Gholamreza; Noormohammadi, Zahra
• Is Part Of: Fundamental & clinical pharmacology. Volume 35:Number 6(2021)
• Page Start: 1055
• Page End: 1068
• Publication Date: 2021-06-16
• Subjects: capsid protein -- HPV vaccine -- in silico analysis -- in vivo studies -- TLR4; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12690
• Languages: English
• ISSNs: 0767-3981

Abstract

Abstract: Different types of cancer including cervical (>90%), anal (~88%), vaginal (~40%), and penile (~40%) cancers are associated with human papillomaviruse (HPV) infections. Three prophylactic vaccines (Cervarix, Gardasil, and Gardasil‐9) were approved to provide immuno‐protection against certain types of HPVs. Currently, next‐generation HPV vaccines such as L1/L2‐based vaccines are being developed to provide broad‐type HPV protection. In this study, we introduced a comprehensive framework for design of L1/L2 polyepitope‐based HPV vaccine candidate. This framework started with protein sequence retrieval and followed by conservancy analysis between high‐risk HPVs, MHC‐I and MHC‐II epitope mapping, and B‐cell and T‐cell epitope mapping. Subsequently, we performed Tap transport and proteasomal cleavage, population coverage, antigenicity, allergenicity and cross‐reactivity. After that, peptide‐MHCI/II flexible docking and comprehensive conservancy analysis against all HPV types were carried out. The next steps were prediction of interferon‐gamma and interleukin‐10 inducing epitopes, epitope selection and construct design, tertiary structure prediction, refinement and validation, discontinuous B‐cell epitope prediction, vaccine‐TLR4 molecular docking, and codon optimization. Our data showed that two designed vaccine constructs harboring 8 L1 peptides or 7 L2 peptides, individually were highly conserved between all well‐known HPV types. In addition, the combination of in silico / in vivo approaches indicated the potential ability of L1 and L2 polyepitope constructs for development of next generation prophylactic/therapeutic HPV vaccine.