Feline Model of Acute Nipah Virus Infection and Protection with a Soluble Glycoprotein-Based Subunit Vaccine

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID 50 ) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID 50 of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.

Pteropid Bats are Confirmed as the Reservoir Hosts of Henipaviruses: A Comprehensive Experimental Study of Virus Transmission

“…Twenty wild-caught adult Pteropus alecto bats from Queensland, Australia (12 pregnant females [Bats [1][2][3][4][5][6][7][8][9][10][11][12], five non-pregnant females [Bats [13][14][15][16][17], and three males [ ) and eight wild-caught adult P. vampyrus bats from Malaysia (four non-pregnant females [Bats [21][22][23][24] and four males [ ) were used in these experiments. Pteropus alecto was chosen because its distribution overlaps the locations where HeV outbreaks have occurred and it is the most abundant species of flying fox in Australia.…”

“…A VNT was used, with either 100 TCID 50 NiV or 100 TCID 50 HeV and Vero cells as previously described. 7 Serum neutralizing titers were recorded as the reciprocal of the serum dilution. Positive and negative controls and a back-titration of the virus were included in each test.…”

“…Samples collected during the study and tissues collected aseptically at postmortem were assayed for the detection of henipavirus genome by TaqMan assay as previously described. 7,8 Primers and TaqMan probe to detect HeV genome and NiV genome were designed from the N gene sequence of HeV (Genbank accession no. AF017149) and NiV (Genbank accession no.…”

Henipavirus: A Review of Laboratory Animal Pathology

“…8,11,40,43,44,47 Some of the recent human NiV cases in Bangladesh were primarily respiratory rather than encephalitic. 5,34,47,49,50 The National Institute of Allergy and Infectious Biodefense Research Agenda classified NiV as a BSL-4 and category C priority pathogen. 7 Risk factors for NiV transmission are human-tohuman contact, contact with infected animals, food-borne transmission, and nosocomial transmission.…”

Nipah Virus

“…Swiss mice inoculated either by the intranasal or the intraperitoneal routes do not develop clinical signs, but NiV antibodies can be produced after repeated infection [55]. However, NiV can be lethal if administered intracranially into suckling mice [58].…”