In-silico design of an epitope-based vaccine against Human Norovirus

Abstract

Background: Every year, noroviruses cause about 20% of endemic and 50% of food-borne acute gastroenteritis in all age groups worldwide, causing ∼700 million illnesses and >200,000 deaths mainly in young children and the elderly. Moreover has emerged as the mainly cause of severe childhood diarrhea in countries that include rotavirus in its vaccination national card like Mexico is. Nowadays, reverse vaccinology is use for the predicting epitopes and identify suitable peptide targets for eventual development of vaccines. In this study, a computational approach was carried out to identify an epitope-based vaccine candidate against norovirus protein that could be suitable to trigger a significant immune response. Methods and materials: 14 sequences of Human Norovirus were obtained from the NCBI. The aminoacidic consensus sequence was used to predict the T-cell and B-cell epitopes. The whole protein consensus sequence was submitted in the NetCTL server and all the super types T-cell were chosen, whit algorithm of MHC-1 binding, TAP proteins transport efficiency and proteosomal cleavage efficiency were involved to predict overall scores. Epitope conservancy for individual peptides was predicted using the epitope tool from IEDB analysis resource. The results from all these sites were cross-referenced, and common findings were taken as the B-cell epitopes. Results: We found in silico analysis that epitopes denominated LTVP1A, LTVP1E, LTVP2A, LTVP2C and LTTPPB, proved to be able to arise the humoral and cellular immune response. The chosen epitopes could generate an activation of T cells and B cells in the Zapoteca and Taraumara Mexican population. However, the genetic diversity that our country presents and the few records of allelic frequency, complicate the effectiveness of this theoretical vaccine. Nevertheless, does not imply that the selected epitopes can be linked to other alleles, which opens the possibility of being use in other countries besides Mexico. Conclusion: For the first time, epitopes obtained with norovirus aminoacidics sequences were tested for binding against the HLA molecules using in silico vaccinology techniques to verify the binding cleft epitope interaction. Nevertheless, further experiments in vitro and in vivo are required to validate this proposal, as well as to assess their potential design of new norovirus vaccines.