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A bioinformatic approach to check the spatial epitope structure of an immunogenic protein coded by DNA vaccine plasmids.

Posted by on in 2015
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  • Ghaemi Bafghi M1Bassami MR2Hashemi Tabar GR3Saberi MR4Haghparast AR5Dehghani H6. 2015. J Theor Biol. 380:315-20. doi: 10.1016/j.jtbi.2015.04.030. Epub 2015 May 21.
  • 1Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: ghaemi100@yahoo.com.
  • 2Department of Clinical Sciences and Division Of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Post code. 9177948974, Iran; Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: bassami@um.ac.ir.
  • 3Department of Pathobiology and Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: hashemit@um.ac.ir.
  • 4School of Pharmacy, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. Electronic address: saberimr@mums.ac.ir.
  • 5Department of Pathobiology and Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: haghparast@ferdowsi.um.ac.ir.
  • 6Department of Basic Science, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: dehghani@um.ac.ir.

Abstract

In this study, we used an approach to check the Hemagglutinin antigen-antibodies interactions after fusion of one or two gene segments to Hemagglutinin gene in some influenza DNA vaccines. We designed different DNA vaccine constructs containing Hemagglutinin 9 (H9) gene fused to four or eight 29 amino acids of C3d (4/8P29C3d) and/or 3, 4 domains of the Fc part of IgY (FcIgY) coding sequences. As there are receptors for P29C3d and FcIgY on the immune cells, fused H9 are targeted to these cells. Three dimensional (3D) structures of the DNA vaccine coded proteins were modeled and docked with two antibodies (1KEN, 1QFU) to evaluate the effect of the H9 gene fusion to the other gene segments (4, 8 P29C3d and FcIgY) on the interaction of two H9 spatial epitopes. Also, we docked DNA vaccine proteins containing Fc IgY to its receptor (CHIR AB1) and compare interaction affinity of Fc IgY alone with affinity of DNA vaccines containing Fc IgY. The average of 1KEN and 1QFU interface scores were 94.89 and 93.09% of H9 DNA vaccine-antibodies interface scores, respectively. These percentages showed a little change in the H9 immunogenic parts. Also, because of spatial freedom of H9 part in all DNA vaccine proteins, added parts may not interfere with antibody-antigen interactions. Once, H9+FcIgY and CHIR AB1 affinity decreased in comparison with affinity of Fc IgY alone and CHIR AB1, affinity of H9+8P29C3d+FcIgY and CHIR AB1 increased to 132%. So, this would be expectable that despite of loss of affinity in H9 and its antibodies in the H9+8P29C3d+FcIgY, dramatic increase of Fc IgY and CHIR AB1 affinity in this group, could repair the loss of H9 affinity and may lead to a better immunogenicity.

Copyright © 2015. Published by Elsevier Ltd.

KEYWORDS:

3D structure; DNA vaccine; Docking; Modeling; Targeting

PMID:
 
26002993
 
[PubMed - in process]
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