DNA vaccination with a single-plasmid construct coding for viruslike particles protects mice against infection with a highly pathogenic avian influenza A virus.

Background: With seasonal outbreaks affecting millions of people each year and devastating pandemics, human influenza is a major health concern. The pandemic threat includes highly pathogenic avian influenza viruses (HPAIVs) that gained the ability to infect humans in Asia and quickly spread throughout the world. Major concerns have been raised regarding today's vaccine production systems against influenza viruses, and new strategies to design efficient vaccines are under intensive investigation.

Methods: We demonstrated elsewhere that viruslike particles (VLPs) incorporating HPAIV hemagglutinin induce strong humoral immune response when injected in mice. In the current study, we evaluated a novel strategy that combines the immunogenicity of influenza VLPs and the advantages of DNA vaccines.

Results: We developed minimal expression vectors encoding all genetic information necessary to produce H7N1 influenza VLPs. We showed that mice vaccinated with small DNA amounts developed specific, high-titer neutralizing antibodies against homologous H7N1 strain and were protected against lethal doses of an antigenically distinct H7N7 HPAIV. Moreover, using some of these constructs, we were able to raise cross-neutralizing antibodies against an unrelated H5N1 HPAIV.

Conclusions: DNA vaccination with constructs coding for influenza VLP production is a promising strategy to induce protection against different influenza viruses.