Prospects for Development of a Marker Vaccine and Companion Diagnostic Test for Nipah Virus

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Prospects for Development of a Marker Vaccine and
Companion Diagnostic Test for Nipah Virus

• James A. Roth, DVM, PhD
• Center for Food Security and Public Health
• College of Veterinary Medicine
• Iowa State University

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Nipah Virus Outbreak

• 1998-1999, Malaysia
• Respiratory and neurologic syndrome in swine
• Encephalitis in humans
• More than 250 cases
• More than 100 deaths
• Initially mistaken for Japanese encephalitis
• Discovered new Paramyxovirus

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Nipah Virus

• Virus isolated in March 1999
• Quick national response with international
  assistance
• 1.1 million pigs culled (out of 2.4 million
  total)
• No new cases in Malaysia since 1999

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Reservoir

• Flying foxes (fruit bats)
• Carry the virus
• Are not affected
• Virus found in
• Urine
• Partially eaten fruit
• Migratory

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Photo courtesy of James Roth, Iowa State
University
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Nipah Field Investigations- Malaysia
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Nipah Virus in Bangladesh

• Outbreaks of respiratory disease, high fever,
  unconsciousness, vomiting, headache
• 2002 to present
• Confirmed to be Nipah virus infection by CDC
• Believed to be oral transmission from
  contaminated fruit

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Rational Design of DIVA Vaccine for Nipah Virus

• Vaccine
• Live virus vector expressing the Nipah F and G
  genes
• Companion Diagnostic Test
• ELISA test for antibody vs Nipah N protein

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Major Challenges for Nipah Vaccine Development

• Biosafety level 4 pathogen
• Access to viral genetic material
• Foreign animal disease
• Recombinant vaccine work in BL2 lab and BL3 Ag
  animal facility
• USDA Import permits
• ISU IBC and IACUC approvals
• USDA APHIS Center for Veterinary Biologics
  approval for vaccine transport
• Permission of State Veterinarian
• Proprietary rights to vaccine vectors
• Funding

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Nipah Virus Vaccine and Companion Diagnostic Test
Development

• Collaborative project between
• ISU College of Veterinary Medicine
• Veterinary Research Institute of Malaysia
• US Centers for Disease Control and Prevention
• USDA Plum Island Animal Disease Center
• USDA APHIS National Veterinary Services
  Laboratories
• Merial Animal Health
• Canadian Food Inspection Agency

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Recombinant Nipah Virus Vaccines Protect Pigs
Against Challenge

• Weingartl, et al, Journal of Virology
  807929-7938, 2006

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Experimental Design

• Four groups of four pigs each
• Controls
• ALVAC F (108 PFU) at 5 and 7 weeks of age
• ALVAC G (108 PFU) at 5 and 7 weeks of age
• ALVAC FG (108 PFU) at 5 and 7 weeks of age
• All pigs challenged (IN, 2.5 105 PFU) with Nipah
  virus in BSL 4 at 8 to 9 weeks of age, necropsied
  6 or 7 days later

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Antibody titers to Nipah virus determined by ELISA
Weingartl et al, J Virol 807929-7938, 2006
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ALVAC-G and ALVAC FG vaccinated pigs had no
detectable virus (rRT-PCR) in pharyngeal washes
or nasal secretions after challenge
Weingartl et al, J Virol 807929-7938, 2006
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ALVAC FG vaccinated pigs had no detectable virus
(rRT-PCR) in tissue homogenates after challenge
Weingartl et al, J Virol 807929-7938, 2006
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Conclusions

• ALVAC canarypox vectored Nipah F and G vaccine
  appears to be a promising vaccine for swine and
  has potential as a vaccine for humans

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Questions?
The Gentle Doctor by Christian Peterson