Abstract
The direct transmission of avian influenza viruses to human and increasing drug resisted strains posing new threats for public health. Therefore, development of efficient vaccines is needed to generate protective and persistent immunity to the viruses. Three motifs of Mx protein sequence in human, mouse and poultry located in interferon induced (GTP ase) domain were candidate as biologic adjuvant for enhancing the immune responses against influenza virus. Chimera proteins composed with the conserved HA2 subunit of influenza virus and the Mx motifs named HA2/Mx were modeled and evaluated by in silico analysis includes bioinformatics algorithms in order to explore biological characteristics of these peptides. Amongst the predicted models, HA2/Mx1 peptide showed the better results following protein structures prediction, antigenic epitopes determination and model quality evaluation. Comparative homology modeling was performed with Swiss Model and the model was validated using ProSA. Epitope predictions revealed the construct could induce both B and T cell epitopes that expect a high immune response. Taken together, these data indicate that the HA2/Mx1 chimera peptide can be potentiated for developing an adjuvant-fused influenza vaccine capable of stimulating effective immune response.
Highlights
Influenza virus subtypes cause a wide spectrum of symptoms ranging from mild illness to fatal disease in bird and mammalian species
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
Summary
Influenza virus subtypes cause a wide spectrum of symptoms ranging from mild illness to fatal disease in bird and mammalian species. Development HA-based vaccine is often difficult to attain due to emergence variants that have undergone sufficient antigenic drift in HA1 globular head to evade existing antibody responses.[13,14] It has been shown that HA2 is highly conserved as compared to HA1 subunit and antibodies recognizing stalk domain of the subunit neutralize the virus and provide sufficiently protection against infection and do cross-react with the HA of other subtypes.[15,16,17] Generally enhanced and directed immune responses to viral vaccine can be achieved by using adjuvants. Prediction of structures, properties, functions and solvent accessibility of proteins plays a crucial role in determining antigenicity and immunogeneicity 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
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