title: Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides protection against Nipah virus disease for over 12 months.
abstract: BACKGROUND
  Nipah virus (NiV) is a zoonotic virus belonging to the henipavirus genus in the family Paramyxoviridae. Since NiV was first identified in 1999, outbreaks have continued to occur in humans in Bangladesh and India on an almost annual basis with case fatality rates reported between 40% and 100%.
  
  
  METHODS
  Ferrets were vaccinated with 4, 20 or 100 μg HeVsG formulated with the human use approved adjuvant, CpG, in a prime-boost regime. One half of the ferrets were exposed to NiV at 20 days post boost vaccination and the other at 434 days post vaccination. The presence of virus or viral genome was assessed in ferret fluids and tissues using real-time PCR, virus isolation, histopathology, and immunohistochemistry; serology was also carried out. Non-immunised ferrets were also exposed to virus to confirm the pathogenicity of the inoculum.
  
  
  RESULTS
  Ferrets exposed to Nipah virus 20 days post vaccination remained clinically healthy. Virus or viral genome was not detected in any tissues or fluids of the vaccinated ferrets; lesions and antigen were not identified on immunohistological examination of tissues; and there was no increase in antibody titre during the observation period, consistent with failure of virus replication. Of the ferrets challenged 434 days post vaccination, all five remained well throughout the study period; viral genome - but not virus - was recovered from nasal secretions of one ferret given 20 μg HeVsG and bronchial lymph nodes of the other. There was no increase in antibody titre during the observation period, consistent with lack of stimulation of a humoral memory response.
  
  
  CONCLUSIONS
  We have previously shown that ferrets vaccinated with 4, 20 or 100 μg HeVsG formulated with CpG adjuvant, which is currently in several human clinical trials, were protected from HeV disease. Here we show, under similar conditions of use, that the vaccine also provides protection against NiV-induced disease. Such protection persists for at least 12 months post-vaccination, with data supporting only localised and self-limiting virus replication in 2 of 5 animals. These results augur well for acceptability of the vaccine to industry.
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia. jackie.pallister@csiro.au
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Pallister
authors.forename: Reuben
authors.initials: R
authors.lastname: Klein
authors.forename: Rachel
authors.initials: R
authors.lastname: Arkinstall
authors.forename: Jessica
authors.initials: J
authors.lastname: Haining
authors.forename: Fenella
authors.initials: F
authors.lastname: Long
authors.forename: John R
authors.initials: JR
authors.lastname: White
authors.forename: Jean
authors.initials: J
authors.lastname: Payne
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Feng
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.forename: Deborah
authors.initials: D
authors.lastname: Middleton
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000825:Animal Structures / Q000473:pathology / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001826:Body Fluids / Q000821:virology; D004195:Disease Models, Animal; D005289:Ferrets; D045464:Henipavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D045405:Nipah Virus / Q000235:genetics / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines