title: Newcastle disease virus vector producing human norovirus-like particles induces serum, cellular, and mucosal immune responses in mice.
abstract: Human norovirus infection is the most common cause of viral gastroenteritis worldwide. Development of an effective vaccine is required for reducing norovirus outbreaks. The inability to grow human norovirus in cell culture has hindered the development of live-attenuated vaccines. To overcome this obstacle, we generated a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We compared two different NDV vectors, a conventional rNDV vector and a modified rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed that the modified vector replicated to higher titers and expressed higher levels of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs than did the conventional vector. We further demonstrated that the VP1 protein produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that are morphologically similar to baculovirus-expressed VLPs. Evaluation of their immunogenicity in mice showed that the modified rNDV vector induced a higher level of IgG response than those induced by the conventional vector and by the baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass antibody for the Th1 response, and specifically, high levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) were detected in splenocytes. In addition, the modified rNDV vector induced a higher level of fecal IgA response in mice than did baculovirus-expressed VLPs. Our findings suggest that the rNDV vector is an efficient system to produce cost-effective VLPs in embryonated chicken eggs and has the potential to be used as a live-attenuated vaccine in humans.
  
  
  OBJECTIVE
  Noroviruses are the major cause of viral gastroenteritis worldwide. Currently, effective vaccines against norovirus infection are not available. In this study, we have evaluated Newcastle disease virus (NDV) as a vaccine vector for norovirus. Our results suggest that NDV can be used not only as a cost-effective method for large-scale production of norovirus-like particle vaccines but also as a live-attenuated vectored vaccine.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
authors.forename: Shin-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
authors.forename: Shun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, DHHS, Bethesda, Maryland, USA.
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Green
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA ssamal@umd.edu.
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002642:Chick Embryo; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009522:Newcastle disease virus / Q000235:genetics*; D029322:Norovirus / Q000235:genetics / Q000276:immunology*; D044967:Serum / Q000737:chemistry; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D016207:Cytokines; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines