Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses

Abstract

Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1 (HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte (CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin (HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.

In Silico Analysis of HA2/Mx Chimera Peptide for Developing an Adjuvanted Vaccine to Induce Immune Responses Against Influenza Viruses

“…The majority of available in silico methods for predicting B-cell immunogenic regions focus on linear epitopes and are based on several amino acid-based propensity scales, including hydrophilicity, solvent accessibility, secondary structure, flexibility, and antigeneicity. 23,29,32 The total residues lying in HA2/Mx1 B cell epitopes were differ from other constructs. Nearly half of amino acid residues in each predicted B cell epitope belonging to different antigenic regions were hydrophobic and the common residues were L, E, A, and V. Since such amino acid residues do not directly contribute to the interaction with antibodies, the surface structures of antigenic sites that are accessible for antibodies were detected.…”

“…Recently many approaches have been applied to introduce a proper adjuvant for enhancing immunity against influenza. [21][22][23][24] However, some post vaccination adverse reactions frequently occurs in recipients. This study was based on the idea of introducing a biological adjuvant to reduce the frequency of the reactions by using in silico prediction, which can save the expense of synthetic peptides and the working time.…”

“…Each of the motifs was ligated to the C-teriminus of HA2 peptide by EAAAK linker that provide structural flexibility, improving protein stability and increasing biological activity. 23,28 The ability of the chimera proteins in induction of immune responses against influenza infection was evaluated subsequently. Prediction of secondary structure of the peptides (Figure 1) was shown the high percentage of helices in their structure makes HA2/Mxs more flexible for folding, which might increase protein interactions.…”

“…[18][19][20] The ability of molecular adjutants such as cytokines, bacterial derivatives and immune system regulator proteins to improve the immunogenicity of vaccines as a novel strategy is under evaluation. [21][22][23][24][25][26] Here we explore the idea of using host cellular protein to elicit immune responses against influenza virus and choose Mx protein which belongs to the class of dynamin-like large guanosine triphosphatases (GTPases) and involves in interferon induction and immune system regulation. 26,27 We focus on details of viral HA2 and cellular Mx interactions for possibly induction immunity against influenza infection using computational chemistry and bioinformatics tools.…”

“…Such results are used in a wide range of applications in molecular biology, medical science and drug and vaccine design. 23,28,29 The in silico study was designed based on comparative modeling techniques to predict the structure, properties and functions of HA2/Mx chimera protein constructs to candidate an efficient gene vaccine against influenza infection.…”