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Design of a Synthetic Long Peptide Vaccine Targeting HPV-16 and -18 Using Immunoinformatic Methods
Alexandru Tîrziu1, Speranța Avram2, Leonard Madă3
1Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania.
Pharmaceutics
|July 29, 2023
Summary
This study introduces a novel synthetic long peptide (SLP) vaccine to target existing human papillomavirus infections and precancerous cervical lesions. The SLP vaccine is designed to elicit strong T cell responses, offering a new strategy beyond prophylactic vaccines.
Area of Science:
- Immunology
- Vaccinology
- Oncology
Background:
- Human papillomavirus (HPV) types 16 and 18 are primary causes of cervical cancer.
- Current prophylactic vaccines, based on virus-like particles (VLPs), do not clear existing HPV infections.
- Individuals with persistent HPV infections face an elevated risk of neoplastic transformation.
Purpose of the Study:
- To develop an alternative vaccine strategy for HPV-infected individuals, including those with precancerous lesions.
- To design a synthetic long peptide (SLP)-based vaccine capable of stimulating robust CD8+ and CD4+ T cell responses.
- To assess the safety, efficacy, and population coverage of the proposed SLP vaccine.
Main Methods:
- Designing SLP constructs incorporating HLA class I and class II restricted epitopes predicted by NetMHCPan and NetMHCIIPan.
- In silico analysis for allergenicity and toxicity of SLPs.
- Population coverage analysis using IEDB allele sets.
- 3D structure prediction using Rosetta and assessment with PROCHECK and QMEAN4.
- Molecular docking with toll-like receptor 2 (TLR2) and molecular dynamics studies.
Main Results:
- In silico studies indicated SLPs were non-allergenic and non-toxic.
- High population coverage was predicted: 98.18% for class I and 99.81% for class II epitopes.
- Rosetta predicted good quality 3D models for SLPs.
- Molecular docking suggested potential intrinsic TLR2 agonist activity.
- Molecular dynamics indicated good stability and favorable thermodynamic properties for SLPs.
Conclusions:
- The developed SLP vaccine is a promising candidate for treating existing HPV infections and associated precancerous lesions.
- The vaccine design targets both CD8+ and CD4+ T cells for a comprehensive immune response.
- In silico and computational analyses support the safety, stability, and broad population applicability of the SLP vaccine.
