FIELD: bioinformatics; immunology.
SUBSTANCE: described is a method for in silico identification and selection of immunogenic highly conserved linear epitopes of influenza virus proteins, wherein a) said linear epitopes of viral proteins are selected so that they stimulate both branches of acquired immunity, including humoral immunity and cellular immunity, wherein, if at step (a) such epitopes are selected, b) among the epitopes of viral proteins selected at step (a), highly conserved CD8+ and CD4+ T-cell and highly conserved B-cell epitopes are selected, wherein selection of highly conserved CD8+ and CD4+ T-cell and highly conserved B-cell epitopes includes: b1) making multiple alignment of sequences of amino acid residues of epitopes of viral proteins selected at step (a); b2) evaluating the conservatism of said epitopes of viral proteins, wherein conservatism of said epitopes at step (b2) is carried out by determining the number of types of amino acid residues k*, occurring in this alignment column, wherein k* is calculated by formula k* = 2s (1), where S is the information entropy of the corresponding column, determined by the formula where pi is the frequency of occurrence of the i-th amino acid residue in the analyzed alignment column, k is the number of all types of residues found in the analyzed alignment column, wherein the i-th amino acid residue in the alignment column is considered to be conservative if condition 1 ≤ki* < 1.5 is satisfied for it, and then c) mapping highly conserved B-cell epitopes, selected at step (b), on X-ray structural analysis data of antigen to check the condition of their availability for antibodies, and if at step (a) such epitopes are not found or are not selected, d) performing bioinformatic prediction for CD8+ and CD4+ T-cell and for B-cell epitopes, thus obtaining a set of epitopes characterized by a given binding score, after which e) steps (b)–(c) are performed to the set of epitopes obtained at step (d), thus obtaining a final set of immunogenic highly conserved linear epitopes of viral proteins. Described is a recombinant expression vector coding a polypeptide composed of epitopes identified by the described method, wherein said polypeptide has SEQ ID NO: 16, SEQ ID NO: 17 or SEQ ID NO: 20. Disclosed is a vaccine composition for immunizing vertebrates against influenza viruses, containing a recombinant expression vector and an immunologically acceptable carrier. Disclosed is a method of vertebrate vaccination against influenza viruses, where said method involves administering to said vertebrate an immunologically effective amount of the vaccine composition.
EFFECT: invention provides selection of epitopes of viral proteins suitable for creation of vaccines of wide spectrum of action.
9 cl, 4 dwg, 17 tbl, 4 ex
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Authors
Dates
2024-02-21—Published
2022-02-15—Filed