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

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. Nipah Virus Outbreak. 1998-1999, Malaysia

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

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  1. 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

  2. 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

  3. 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

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

  5. Photo courtesy of James Roth, Iowa State University

  6. Nipah Field Investigations- Malaysia

  7. 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

  8. 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

  9. 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

  10. 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

  11. Recombinant Nipah Virus Vaccines Protect Pigs Against Challenge Weingartl, et al, Journal of Virology 80:7929-7938, 2006

  12. 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 F&G (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

  13. Antibody titers to Nipah virus determined by ELISA Weingartl et al, J Virol 80:7929-7938, 2006

  14. ALVAC-G and ALVAC F&G vaccinated pigs had no detectable virus (rRT-PCR) in pharyngeal washes or nasal secretions after challenge Weingartl et al, J Virol 80:7929-7938, 2006

  15. ALVAC F&G vaccinated pigs had no detectable virus (rRT-PCR) in tissue homogenates after challenge Weingartl et al, J Virol 80:7929-7938, 2006

  16. 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

  17. Questions? The Gentle Doctor by Christian Peterson

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