Designing of CD8 and CD4 T cell epitope based vaccine by targeting whole genome of Asian subtype HPV 52 isolates

SATYAVANI Kaliamurthi (TALK)

institution: Henan University of Technology

abstract:

Designing of CD8+ and CD4+ T-cell epitope based vaccine by targeting whole genome of Asian subtype HPV 52 isolates

Satyavani Kaliamurthi1, Gurudeeban Selvaraj1, Keren Gu1,2, Dong-Qing Wei1,3

1Center of Interdisciplinary Sciences-Computational Life Sciences, College of Food Science and Engineering, Henan University of Technology, Zhengzhou, 450001, China

2College of Chemistry, Chemical Engineering and Environment, Henan University of Technology, Zhengzhou, 450001, China

3The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

Corresponding Author: dqwei@sjtu.edu.cn

Background and aim: Human papillomavirus (HPV) is the sexually transmitted etiologic agent causes high-grade of developing cervical lesions and cervical cancer in women around the world. Recent studies reported HPV52, one of the prevalent subtype in Asia, especially in southwest China. The commercial vaccines (Gardasil and Cervarix) predominantly consider HPV16 and HPV18 strains associated with cervical cancer. Therefore, we aimed to predict multi-epitope based vaccine by targeting whole genome sequence of HPV52 using different immuno-informatics and machine learning tools. Results: Initially, the whole proteome of HPV52 (L1, L2, E1, E2, E6, and E7) were retrieved from UniProt database and perused to identify the most immunogenic protein. The non-allergenic and antigenic proteins were selected and used for the prediction of epitopes which induces both B-cell and T-cell mediated immunity. In total, 650 promiscuous most putative MHC class I binders was predicted from the antigenic protein sequences of HPV52 by using HLAPred. Among the 650 epitopes, only 362 immunogenic epitopes were selected to assess anticancer property. The support vector machine based machine-learning tool identified 130 potent anticancer. In addition, only 32 CD8+ T cells epitopes were predicted which has to induce both T cell and B cell-mediated immune responses. Then, the pooled peptides with restricted HLA alleles showed high population coverage in Europe (99.15%), East Asia (98.80%), Northeast Asia (95.89%), Southeast Asia (95.81%), South Asia (95.51%) and Southwest Asia (94.78%) respectively. Further, molecular docking studies explained the inter-molecular interaction between the predicted epitopes with HLA alleles. The conserved HPV52 epitopes provide broader protection across multiple high-risk strains HPV (16, 18, 31, 33, 35, 39, 45, 56, 58, 59, 68, and 73) through 100% cross-reactivity. In conclusion, the further experimental screening will confirm the clinical utility of predicted epitope-based vaccine for HPV52 mediated cervical cancer incidents.

Keywords: cervical cancer; cellular immunity, linear epitopes; PEP-FOLD; HPV52;