In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever

Abstract

Lassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence-and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T-and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines.Lassa virus (LASV), a member of the Arenaviridae 1 , is an ambisense RNA virus that causes a severe hemorrhagic Lassa fever in humans. LASV is endemic, particularly in the West African countries of Sierra Leone, The Republic of Guinea, Nigeria, and Liberia 2,3 . The transmission of LASV to humans occurs through the urine or feces of infected Mastomys rats and the virus spreads human-to-human through direct contact with the blood, urine, feces, or other bodily secretions of an infected person. LASV can be fatal and no approved effective therapeutics are currently available. The development of therapeutics such as antibodies and vaccines for the treatment of LASV is therefore of significant urgency 4-6 .Of the four proteins that are encoded by the two RNA segments of the LASV genome, the glycoprotein (GP) is the only protein on the viral surface. GP results from the cleavage of a 75 kDa precursor polypeptide, GPC by signal peptidase and then further glycosylated and processed into GP1 and GP2 7 . GP1 is the receptor-binding subunit, and GP2 is the membrane-spanning fusion subunit 8-10 . The virion envelope protein spikes are composed of three heterotrimers, with each heterotrimer containing signal peptide, GP1, and GP2 11,12 , shown in Fig. 1. A chalice-like GP trimer interacts with receptors on the cell surface, for example matriglycan, which mediates the entry of the virus into the host cell. In addition, the GP also interact with ERGIC-53 in the exocytic pathway, which helps to form infectious virions 13 . GP is considere...

Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein

“…While BepiPred and ElliPro predict many potential regions, glycan shielding effectively leaves only a few regions as potential epitope candidates (Figure a,b). As more sophisticated preceding works, , we can recover just about all experimentally known epitopes, demonstrating the potential of this approach. Two of the known epitopes (GPC-A: residues 272–285; GPC-B: residues 361–375) have low prediction scores.…”

Significance of the RBD mutations in the SARS-CoV-2 Omicron: from spike opening to antibody escape and cell attachment

“…To explore the antigenic shifts due to the mutations, we first identified the RBD epitopes using various MHC-I and MHC-II prediction methods as well as sequence and structure-based B-Cell epitope prediction methods as described in the Supporting Information and used a consensus approach 15 to select the epitopes for further analysis. The consensus epitopes that contain the mutations in RBD are given in the Supplementary Table S2, and all of the predicted epitopes (sequence-based and structure-based) are listed in Table S3, S4, S5 and S6.…”

Combination of highly antigenic nucleoproteins to inaugurate a cross-reactive next generation vaccine candidate against Arenaviridae family

“…Nucleoprotein (NP) specific CD8þ T cells play a major role in virus control and immune stimulation in the host [59]. Barale et al (2020) explored Lassa virus glycoprotein to identify candidate epitopes in a previous study [60]. However, this study focused on NP protein and the prediction of conserved epitopes in this protein is new.…”