Abstract
Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 not only cause a devastating disease in domestic chickens and turkeys but also pose a continuous threat to public health. In some countries, H5N1 viruses continue to circulate and evolve into new clades and subclades. The rapid evolution of these viruses represents a problem for virus diagnosis and control. In this work, recombinant vesicular stomatitis virus (VSV) vectors expressing HA of subtype H5 were generated. To comply with biosafety issues the G gene was deleted from the VSV genome. The resulting vaccine vector VSV*ΔG(HA) was propagated on helper cells providing the VSV G protein in trans. Vaccination of chickens with a single intramuscular dose of 2×108 infectious replicon particles without adjuvant conferred complete protection from lethal H5N1 infection. Subsequent application of the same vaccine strongly boosted the humoral immune response and completely prevented shedding of challenge virus and transmission to sentinel birds. The vaccine allowed serological differentiation of infected from vaccinated animals (DIVA) by employing a commercially available ELISA. Immunized chickens produced antibodies with neutralizing activity against multiple H5 viruses representing clades 1, 2.2, 2.5, and low-pathogenic avian influenza viruses (classical clade). Studies using chimeric H1/H5 hemagglutinins showed that the neutralizing activity was predominantly directed against the globular head domain. In summary, these results suggest that VSV replicon particles are safe and potent DIVA vaccines that may help to control avian influenza viruses in domestic poultry.
Highlights
Outbreaks of highly pathogenic influenza viruses (HPAIV) in chickens and turkeys have led to profound economical losses in many regions, including Italy, The Netherlands, Egypt, Mexico, and Southeast Asia [1,2]
Non-transmissible vesicular stomatitis virus (VSV) vectors were generated by replacing the VSV glycoprotein G gene with either the hemagglutinin (HA) gene of A/chicken/Yamaguchi/7/2004 (H5N1), a highly pathogenic avian influenza virus (HPAIV), the HA gene of A/duck/Hokkaido/Vac-1/2004 (H5N1), a lowpathogenic avian influenza virus (LPAIV) [24], or the enhanced green fluorescent protein gene (Fig. 1a)
To facilitate virus detection and titration, the enhanced green fluorescent protein (eGFP) reporter protein was expressed from an additional transcription cassette downstream of the HA genes
Summary
Outbreaks of highly pathogenic influenza viruses (HPAIV) in chickens and turkeys have led to profound economical losses in many regions, including Italy, The Netherlands, Egypt, Mexico, and Southeast Asia [1,2]. A common feature of HPAIV is the presence of a multi-basic cleavage site that is recognized by furinlike proteases [3]. As a consequence of the ubiquitous expression of these proteases, HPAIVs cause systemic multi-organ disease in poultry. This disease is historically known as ‘‘fowl plague’’ reflecting its rapid spread and high mortality rates of up to 100%. Several AIV subtypes could potentially mutate to become highly pathogenic [4], only HPAIV of subtypes H5 and H7 have been detected in nature so far. It is generally believed that LPAIVs occasionally evolve into HPAIVs when circulating in domestic poultry [1,5]
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