Abstract
Recombinant Newcastle disease viruses (rNDV) have been used as bivalent vectors for vaccination against multiple economically important avian pathogens. NDV-vectored vaccines expressing the immunogenic H5 hemagglutinin (rNDV-H5) are considered attractive candidates to protect poultry from both highly pathogenic avian influenza (HPAI) and Newcastle disease (ND). However, the impact of the insertion of a recombinant protein, such as H5, on the biological characteristics of the parental NDV strain has been little investigated to date. The present study compared a rNDV-H5 vaccine and its parental NDV LaSota strain in terms of their structural and functional characteristics, as well as their recognition by the innate immune sensors. Structural analysis of the rNDV-H5 demonstrated a decreased number of fusion (F) and a higher number of hemagglutinin-neuraminidase (HN) glycoproteins compared to NDV LaSota. These structural differences were accompanied by increased hemagglutinating and neuraminidase activities of rNDV-H5. During in vitro rNDV-H5 infection, increased mRNA expression of TLR3, TLR7, MDA5, and LGP2 was observed, suggesting that the recombinant virus is recognized differently by sensors of innate immunity when compared with the parental NDV LaSota. Given the growing interest in using NDV as a vector against human and animal diseases, these data highlight the importance of thoroughly understanding the recombinant vaccines’ structural organization, functional characteristics, and elicited immune responses.
Highlights
Newcastle disease (ND) and highly pathogenic avian influenza (HPAI) are two highly contagious and economically devastating notifiable poultry diseases [1,2]
Immunogold labeling confirmed the presence of H5 at the surface of Recombinant Newcastle disease viruses (rNDV)-H5 (4.6 ± 0.7 gold particles/virion), while a background level of H5 labeling of
The neutralization curves obtained using the anti-F monoclonal antibody were similar for both viruses (Figure 1b, left panel), while NDV LaSota was neutralized at 83% by anti-HN monoclonal antibody at the concentration of 0.63 μg/mL, which was significantly higher than the 17% of neutralization of rNDV-H5 at the same monoclonal antibodies (mAbs) concentration (Figure 1b, right panel)
Summary
Newcastle disease (ND) and highly pathogenic avian influenza (HPAI) are two highly contagious and economically devastating notifiable poultry diseases [1,2] The continuous threat they represent to the poultry sector worldwide emphasizes the need for high-level biosecurity measures, strong surveillance strategies, and efficient vaccination programs [3,4,5]. The use of recombinant viral vector-based vaccines expressing one or several foreign genes represents a promising vaccination strategy. The protection afforded by these vaccines is validated by testing their potency following an infection by a virulent pathogen related to the viral vector or the foreign gene expressed, and by identifying the host immune responses elicited. NDV infection is initiated by the attachment of the virus through the binding of hemagglutinin-neuraminidase (HN)
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