Vaccinomic approach for novel multi epitopes vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

BACKGROUND: The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers. RESULTS: The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was - 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stability of the vaccine via Ramachandran plot and ProSA-web servers. Moreover, solubility of the vaccine construct was greater than the average solubility provided by protein sol and SOLpro servers indicating the solubility of the vaccine construct. Disulfide engineering was performed to reduce the high mobile regions in the vaccine to enhance stability. Docking of the vaccine construct with TLR4 demonstrated efficient binding energy with attractive binding energy of - 338.68 kcal/mol and - 346.89 kcal/mol for TLR4 chain A and chain B respectively. Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells and INF-γ. Upon cloning, the vaccine protein was reverse transcribed into DNA sequence and cloned into pET28a(+) vector to ensure translational potency and microbial expression. CONCLUSION: A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.

Immunoinformatics Approach for Multiepitope Vaccine Prediction from H, M, F, and N Proteins of Peste des Petits Ruminants Virus.

BACKGROUND: Small ruminant morbillivirus or peste des petits ruminants virus (PPRV) is an acute and highly contagious viral disease of goats, sheep, and other livestock. This study aimed at predicting an effective multiepitope vaccine against PPRV from the immunogenic proteins haemagglutinin (H), matrix (M), fusion (F), and nucleoprotein (N) using immunoinformatics tools. MATERIALS AND METHODS: The sequences of the immunogenic proteins were retrieved from GenBank of the National Center for Biotechnology Information (NCBI). BioEdit software was used to align each protein from the retrieved sequences for conservancy. Immune Epitope Database (IEDB) analysis resources were used to predict B and T cell epitopes. For B cells, the criteria for electing epitopes depend on the epitope linearity, surface accessibility, and antigenicity. RESULTS: Nine epitopes from the H protein, eight epitopes from the M protein, and ten epitopes from each of the F and N proteins were predicted as linear epitopes. The surface accessibility method proposed seven surface epitopes from each of the H and F proteins in addition to six and four epitopes from the M and N proteins, respectively. For antigenicity, only two epitopes 142PPERV146 and 63DPLSP67 were predicted as antigenic from H and M, respectively. For T cells, MHC-I binding prediction tools showed multiple epitopes that interacted strongly with BoLA alleles. For instance, the epitope 45MFLSLIGLL53 from the H protein interacted with four BoLA alleles, while 276FKKILCYPL284 predicted from the M protein interacted with two alleles. Although F and N proteins demonstrated no favorable interaction with B cells, they strongly interacted with T cells. For instance, 358STKSCARTL366 from the F protein interacted with five alleles, followed by 340SQNALYPMS348 and 442IDLGPAISL450 that interacted with three alleles each. The epitopes from the N protein displayed strong interaction with BoLA alleles such as 490RSAEALFRL498 that interacted with five alleles, followed by two epitopes 2 ATLLKSLAL 10 and 304QQLGEVAPY312 that interacted with four alleles each. In addition to that, four epitopes 3TLLKSLALF11 , 356YFDPAYFRL364 , 360AYFRLGQEM368 , and 412PRQAQVSFL420 interacted with three alleles each. CONCLUSION: Fourteen epitopes were predicted as promising vaccine candidates against PPRV from four immunogenic proteins. These epitopes should be validated experimentally through in vitro and in vivo studies.