Designing a multi-epitope vaccine to provoke the robust immune response against influenza A H7N9

Abstract

A new strain of Influenza A Virus (IAV), so-called "H7N9 Avian Influenza", is the first strain of this virus in which a human is infected by transmitting the N9 of influenza virus. Although continuous human-to-human transmission has not been reported, the occurrence of various H7N9-associated epidemics and the lack of production of strong antibodies against H7N9 in humans warn of the potential for H7N9 to become a new pandemic. Therefore, the need for effective vaccination against H7N9 as a life-threatening viral pathogen has become a major concern. The current study reports the design of a multi-epitope vaccine against Hemagglutinin (HA) and Neuraminidase (NA) proteins of H7N9 Influenza A virus by prediction of Cytotoxic T lymphocyte (CTL), Helper T lymphocyte (HTL), IFN-γ and B-cell epitopes. Human β-defensin-3 (HβD-3) and pan HLA DR-binding epitope (PADRE) sequence were considered as adjuvant. EAAAK, AAY, GPGPG, HEYGAEALERAG, KK and RVRR linkers were used as a connector for epitopes. The final construct contained 777 amino acids that are expected to be a recombinant protein of about ~ 86.38 kDa with antigenic and non-allergenic properties after expression. Modeled protein analysis based on the tertiary structure validation, docking studies, and molecular dynamics simulations results like Root-mean-square deviation (RMSD), Gyration, Root-mean-square fluctuation (RMSF) and Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) showed that this protein has a stable construct and capable of being in interaction with Toll-like receptor 7 (TLR7), TLR8 and m826 antibody. Analysis of the obtained data the demonstrates that suggested vaccine has the potential to induce the immune response by stimulating T and Bcells, and may be utilizable for prevention purposes against Avian Influenza A (H7N9).

In silico design of a promiscuous chimeric multi-epitope vaccine against Mycobacterium tuberculosis

“…HEYGAEALERAG linker was also used to link the CTL epitope subunit to the 10 downstream linear B-cell epitopes linked together by KK linkers. According to previous studies, the KK linker prevents the induction of antibodies into the amino acid sequence resulting from the combination of the two peptides, thereby facilitating the specific display of each peptide to antibody [111] . Finally, a His× 6 tag was attached to the C-terminus of the last linear B-cell epitope for subsequent purification and characterization of the vaccine ( Fig.…”

Multiepitope‐based vaccine design by exploring antigenic potential among leptospiral lipoproteins using comprehensive immunoinformatics and structure‐based approaches

“…The selected regions (containing all types of epitopes) from each protein were joined with GPGPG and AAY linkers. The GPGPG linker is reported to restore the T‐helper response, and AAY prevents the generation of junctional epitope and enhances epitope presentation by HLA alleles 62–64 . The immunogenicity of the vaccine construct was enhanced by incorporating human β‐defensin as an adjuvant to the N‐terminal of the designed vaccine via the EAAAK linker.…”

“…The GPGPG linker is reported to restore the T-helper response, and AAY prevents the generation of junctional epitope and enhances epitope presentation by HLA alleles. [62][63][64] The immunogenicity of the vaccine construct was enhanced by incorporating human β-defensin as an adjuvant to the N-terminal of the designed vaccine via the EAAAK linker. The human β-defensin was chosen, as it serves as both an antimicrobial agent and immunomodulator.…”

Development of a Multi-Epitope Universal mRNA Vaccine Candidate for Monkeypox, Smallpox, and Vaccinia Viruses: Design and In Silico Analyses

“…For the construction of the multi-epitope mRNA vaccine, the epitopes were arranged orderly. B cell epitopes were joined with a flexible linker KK [ 33 , 34 ], while a GGGS linker was used to connect the T cell epitopes [ 35 ]. The leading sequence of tissue plasminogen activator (tPA) that augments the antigen presentation [ 36 ] was used as a signal sequence (MDAMKRGLCCVLLLCGAVFVSPS).…”

“…The incorporation of the amino acid sequence of interleukin 6 (IL-6) was done to enhance the immunogenicity of the vaccine [ 37 ]. The pan-HLA DR binding epitope (PADRE sequence) was connected to the IL-6 sequence via a GGGS linker and to an epitope of the B cell via EAAAK [ 34 , 38 ]. A polyhistidine (6x) tag was placed on the C-terminal of the vaccine sequence for facilitating the fusion protein detection [ 39 ].…”