Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - An immunoinformatics analysis

Highlights

• Viral glycoproteins are always the major targets for vaccine and drug development.

• Immunoinformatics approach significantly reduces time, effort & cost of immunodominant region identification in a protein.

• Promiscuous T cell epitopes conserved in both HSV-1 & 2 major glycoproteins were identified.

• Conserved Linear and conformational B cell epitopes were also identified for the same.

• The study proposes promising immunodominant regions which could be utilized in developing peptide pool based vaccine.

Abstract

Infections due to both HSV-1 and HSV-2 constitute an enormous health burden worldwide. Development of vaccine against herpes infections is a WHO supported public health priority. The viral glycoproteins have always been the major hotspots for vaccine designing. The present study was aimed to identify the conserved T and B cell epitopes in the major glycoproteins of both HSV-1 and HSV-2 via rigorous computational approaches. Identification of promiscuous T cell epitopes is of utmost importance in vaccine designing as such epitopes are capable of binding to several allelic forms of HLA and could generate effective immune response in the host. The criteria designed for identification of T and B cell epitopes was that it should be conserved in both HSV-1 and 2, promiscuous, have high affinity towards HLA alleles, should be located on the surface of glycoproteins and not be present in the glycosylation sites. This study led to the identification of 17 HLA Class II and 26 HLA Class I T cell epitopes, 9 linear and some conformational B cell epitopes. The identified T cell epitopes were further subjected to molecular docking analysis to analyze their binding patterns. Altogether we have identified 4 most promising regions in glycoproteins (2-gB, 1-gD, 1-gH) of HSV-1 and 2 which are promiscuous to HLA Class II alleles and have overlapping HLA Class I and B cell epitopes, which could be very useful in generating both arms of immune response in the host i.e. adaptive as well as humoral immunity. Further the authors propose the cross-validation of the identified epitopes in experimental settings for confirming their immunogenicity to support the present findings.

Introduction

The infections caused by Herpes simplex viruses (HSV) impose an enormous health burden on the world's population commonly causing oral and genital ulcerations. Other serious but less common complications include neonatal infection, encephalitis, keratitis and meningitis. The high prevalence of HSV-2 contributes significantly to the epidemic of Human Immunodeficiency virus (HIV) (Johnston et al., 2016). The global incidence of HSV-2 infection recorded in 2012 was about 417 million in aged between 15 and 49 years with an incidence of 19 million infections per year as estimated by World Health Organization (WHO) (Looker et al., 2015).

As the infections caused by HSV are subclinical, the incidence of the disease and its prevalence data underestimate the impact of the infection. At present the treatment for HSV involves antiviral therapy using acyclovir, valacyclovir or famcyclovir (Johnston et al., 2016). Considering the fact that the current strategies for control of HSV-2 infections are partially effective, there is no permanent cure or treatment available for herpes as virus is known to persist in a latent phase and disease is well known for its recurrence (Gottlieb et al., 2017). Thus, the development of a prophylactic and therapeutic vaccine is urgently needed. The development of a prophylactic vaccine for HSV-1 and HSV-2 is a WHO-supported global public health priority (Sandgren et al., 2016). For an ideal vaccine candidate it should provide immunity against both HSV-1 and HSV-2, and contain both immunodominant T-cell epitopes as well as neutralizing antibody epitopes (Sandgren et al., 2016). Various HSV vaccines have been tried by different research groups and are in different phases of clinical trials, currently there is no commercially available vaccine (Belshe et al., 2012, Belshe et al., 2013).

Keeping the above points under consideration, the present study aimed to identify potential epitopes in the major glycoproteins of HSV, which facilitate virus entry into the cells and could be vaccine targets.