title: Codon optimization of antigen coding sequences improves the immune potential of DNA vaccines against avian influenza virus H5N1 in mice and chickens.
abstract: Highly pathogenic avian influenza viruses are a serious threat to domestic poultry and can be a source of new human pandemic and annual influenza strains. Vaccination is the main strategy of protection against influenza, thus new generation vaccines, including DNA vaccines, are needed. One promising approach for enhancing the immunogenicity of a DNA vaccine is to maximize its expression in the immunized host.
  
  
  
  The immunogenicity of three variants of a DNA vaccine encoding hemagglutinin (HA) from the avian influenza virus A/swan/Poland/305-135V08/2006 (H5N1) was compared in two animal models, mice (BALB/c) and chickens (broilers and layers). One variant encoded the wild type HA while the other two encoded HA without proteolytic site between HA1 and HA2 subunits and differed in usage of synonymous codons. One of them was enriched for codons preferentially used in chicken genes, while in the other modified variant the third position of codons was occupied in almost 100 % by G or C nucleotides.
  
  
  
  The variant of the DNA vaccine containing almost 100 % of the GC content in the third position of codons stimulated strongest immune response in two animal models, mice and chickens. These results indicate that such modification can improve not only gene expression but also immunogenicity of DNA vaccine.
  
  
  
  Enhancement of the GC content in the third position of the codon might be a good strategy for development of a variant of a DNA vaccine against influenza that could be highly effective in distant hosts, such as birds and mammals, including humans.
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland.
authors: Anna
authors: A
authors: Stachyra
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland.
authors: Patrycja
authors: P
authors: Redkiewicz
authors: Mossakowski Medical Research Centre Polish Academy of Sciences, ul., Pawinskiego 5, 02-106, Warsaw, Poland.
authors: Piotr
authors: P
authors: Kosson
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland.
authors: Anna
authors: A
authors: Protasiuk
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland.
authors: Anna
authors: A
authors: Góra-Sochacka
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, Scotland, UK.
authors: Grzegorz
authors: G
authors: Kudla
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul., Pawinskiego 5A, 02-106, Warsaw, Poland. asirko@ibb.waw.pl.
authors: Agnieszka
authors: 0000-0002-5205-2924
authors: A
authors: Sirko
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D002645:Chickens; D003062:Codon; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D005585:Influenza in Birds / Q000517:prevention & control; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011044:Poland; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D003062:Codon; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; C109963:hemagglutinin, avian influenza A virus
keywords: Chickens; DNA vaccine; GC content; H5N1; Influenza; Mice