Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.

Sunanda Baidya,Md Arifuzzaman,Rasel Das,Md Golam Kabir

doi:10.6026/97320630013086

Abstract

Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through “reverse vaccinology” approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.

Highlights

Human papillomaviruses (HPVs) are small in shape, nonenveloped, double stranded DNA viruses whose eight proteins are encoded by approximately 8 kb circular genome [1, 2]
Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18
The HPV genome can be classified into three regions; the long control region (LCR), the early open reading frame (EORF) and the late reading frame (LORF) [3]

Summary

Introduction

Human papillomaviruses (HPVs) are small in shape, nonenveloped, double stranded DNA viruses whose eight proteins are encoded by approximately 8 kb circular genome [1, 2]. The viral ORFs are comprised of three regulatory genes involved in transcription and replication (E1, E2, and E4), three oncogenes (E5, E6, and E7) and two genes encoding for self-assembling proteins, which constitute the viral capsid (L1 and L2) [4]. To date, this virus is reported to cause 99% of cervical cancer [5], 93% of anus [6], 40% of vagina [7], 40% of penis [8], 63% of oropharynx [9] and 51% of vulva cancers [10]. Prevention of this viral infection is of more importance, since it contributes about 85% to global cervical cancer burden [4]

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