Abstract
Human norovirus (HuNoV) is responsible for more than 95% of outbreaks of acute nonbacterial gastroenteritis worldwide. Despite major efforts, there are no vaccines or effective therapeutic interventions against this virus. Chicken immunoglobulin Y (IgY)-based passive immunization has been shown to be an effective strategy to prevent and treat many enteric viral diseases. Here, we developed a highly efficient bioreactor to generate high titers of HuNoV-specific IgY in chicken yolks using a recombinant vesicular stomatitis virus expressing HuNoV capsid protein (rVSV-VP1) as an antigen. We first demonstrated that HuNoV VP1 protein was highly expressed in chicken cells infected by rVSV-VP1. Subsequently, we found that White Leghorn hens immunized intramuscularly with rVSV-VP1 triggered a high level of HuNoV-specific yolk IgY antibodies. The purified yolk IgY was efficiently recognized by HuNoV virus-like particles (VLPs). Importantly, HuNoV-specific IgY efficiently blocked the binding of HuNoV VLPs to all three types (A, B, and O) of histo-blood group antigens (HBGAs), the attachment factors for HuNoV. In addition, the receptor blocking activity of IgY remained stable at temperature below 70 °C and at pH ranging from 4 to 9. Thus, immunization of hens with VSV-VP1 could be a cost-effective and practical strategy for large-scale production of anti-HuNoV IgY antibodies for potential use as prophylactic and therapeutic treatment against HuNoV infection.
Highlights
The virus family Caliciviridae contains five established genera (Norovirus, Sapovirus, Lagovirus, Vesivirus, and Nebovirus) and at least six proposed genera (Recovirus, Valovirus, Bavovirus, Nacovirus, Minovirus, and Salovirus) that infect many different animal species including humans
We first determined whether Recombinant vesicular stomatitis virus (rVSV)-VP1 replicated efficiently in DF-1 cells, which are derived from chicken embryo
We developed a highly efficient bioreactor to produce human norovirus (HuNoV)-specific immunoglobulin Y (IgY) in egg yolks by immunization of white leghorn chickens with recombinant rVSV-VP1
Summary
The virus family Caliciviridae contains five established genera (Norovirus, Sapovirus, Lagovirus, Vesivirus, and Nebovirus) and at least six proposed genera (Recovirus, Valovirus, Bavovirus, Nacovirus, Minovirus, and Salovirus) that infect many different animal species including humans. Most of these agents are enteric pathogens whose replication and chief clinical manifestations are gastroenteritis and potentially life-threatening diarrhea. Examples of these viruses include human norovirus (HuNoV), porcine norovirus, bovine norovirus, human sapovirus, porcine sapovirus, and the recently discovered. HuNoV infection is usually self-limited disease, it is highly contagious, and only a few particles are thought to be sufficient to cause an infection [1,2,7]
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