Abstract
BackgroundHighly 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.MethodsThe 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.ResultsThe 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.ConclusionEnhancement 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0599-y) contains supplementary material, which is available to authorized users.
Highlights
Pathogenic avian influenza viruses are a serious threat to domestic poultry and can be a source of new human pandemic and annual influenza strains
Vaccines against influenza are traditionally produced from viruses propagated in chicken embryos, the first formulations with antigens produced in cell lines are available, for example Flucelvax®
The cells transfected with GK/pCI usually produced about 15–30 % more HA than the cells transfected with K3/pCI, while the HA protein in cells transfected with HAw/pCI was hardly detectable
Summary
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, new generation vaccines, including DNA vaccines, are needed. Vaccines against influenza are traditionally produced from viruses propagated in chicken embryos, the first formulations with antigens produced in cell lines are available, for example Flucelvax®. Stachyra et al Virology Journal (2016) 13:143 disease outbreaks. They guarantee antigens with native structure, identical with those within infection, containing all posttranslational modifications, since they are produced in vivo in host cells. They are safe and no infective form of the pathogen is needed at any step. It is not surprising that several clinical trials of DNA vaccines against influenza are ongoing (http://clinicaltrials.gov/) [5, 6]
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