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Published in: Virology Journal 1/2013

Open Access 01-12-2013 | Research

Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides protection against Nipah virus disease for over 12 months

Authors: Jackie A Pallister, Reuben Klein, Rachel Arkinstall, Jessica Haining, Fenella Long, John R White, Jean Payne, Yan-Ru Feng, Lin-Fa Wang, Christopher C Broder, Deborah Middleton

Published in: Virology Journal | Issue 1/2013

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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.

Literature
  1. Eaton BT, Mackenzie JS, Wang LF: Henipaviruses. In Fields Virology. Edited by: Knipe DM, Griffin DE, Lamb RA, Straus SE, Howley PM, Martin MA, Roizman B. Philadelphia: Lippincott Williams & Wilkins; 2007:1587-1600.
  2. Marsh GA, De Jong C, Barr JA, Smith C, Middleton D, Yu M, Todd S, Foord A, Haring V, Payne J, et al.: Cedar virus: a novel virus isolated from Australian bats. PLoS Pathog 2012, 8: 1-11.View Article
  3. Li Y, Wang J, Hickey AC, Zhang Y, Wu Y, Zhang H, Yuan J, Han Z, McEachern J, Broder CC, et al.: Antibodies to Nipah or Nipah-like viruses in bats, China. Emerg Infect Dis 2008, 14: 1974-1976. 10.3201/eid1412.080359PubMedPubMed CentralView Article
  4. Drexler JF, Corman VM, Gloza-Rausch F, Seebens A, Annan A, Ipsen A, Kruppa T, Muller MA, Kalko EK, Adu-Sarkodie Y, et al.: Henipavirus RNA in African bats. PLoS One 2009, 4: e6367. 10.1371/journal.pone.0006367PubMedPubMed CentralView Article
  5. Baker KS, Todd S, Marsh G, Fernandez-Loras A, Suu-Ire R, Wood JL, Wang LF, Murcia PR, Cunningham AA: Co-circulation of diverse paramyxoviruses in an urban African fruit bat population. J Gen Virol 2012, 93: 850-856. 10.1099/vir.0.039339-0PubMedPubMed CentralView Article
  6. Drexler JF, Corman VM, Muller MA, Maganga GD, Vallo P, Binger T, Gloza-Rausch F, Rasche A, Yordanov S, Seebens A, et al.: Bats host major mammalian paramyxoviruses. Nat Commun 2012, 3: 796.PubMedPubMed CentralView Article
  7. Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK, Ksiazek TG, Rollin PE, Zaki SR, Shieh W, et al.: Nipah virus: a recently emergent deadly paramyxovirus. Science 2000, 288: 1432-1435. 10.1126/science.288.5470.1432PubMedView Article
  8. Pallister J, Middleton D, Broder CC, Wang L-F: Henipavirus vaccine development. Journal of Bioterrorism and Biodefense 2011, S1: 005.
  9. Mahalingam S, Herrero LJ, Playford EG, Spann K, Herring B, Rolph MS, Middleton D, McCall B, Field H, Wang LF: Hendra virus: an emerging paramyxovirus in Australia. Lancet Infect Dis 2012, 12: 799-807. 10.1016/S1473-3099(12)70158-5PubMedView Article
  10. Selvey LA, Taylor R, Arklay A, Gerrard J: Screening of bat carers for antibodies to equine morbillivirus. Communicable Disease Intelligence 1996, 20: 477-478.
  11. Luby SP, Gurley ES, Hossain MJ: Transmission of human infection with Nipah virus. Clin Infect Dis 2009, 49: 1743-1748. 10.1086/647951PubMedPubMed CentralView Article
  12. Khetawat D, Broder CC: A functional henipavirus envelope glycoprotein pseudotyped lentivirus assay system. Virol J 2010, 7: 312. 10.1186/1743-422X-7-312PubMedPubMed CentralView Article
  13. Bonaparte MI, Dimitrov AS, Bossart KN, Crameri G, Mungall BA, Bishop KA, Choudhry V, Dimitrov DS, Wang LF, Eaton BT, Broder CC: Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc Natl Acad Sci USA 2005, 102: 10652-10657. 10.1073/pnas.0504887102PubMedPubMed CentralView Article
  14. Negrete OA, Wolf MC, Aguilar HC, Enterlein S, Wang W, Muhlberger E, Su SV, Bertolotti-Ciarlet A, Flick R, Lee B: Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathog 2006, 2: e7. 10.1371/journal.ppat.0020007PubMedPubMed CentralView Article
  15. Negrete OA, Chu D, Aguilar HC, Lee B: Single amino acid changes in the Nipah and Hendra virus attachment glycoproteins distinguish ephrinB2 from ephrinB3 usage. J Virol 2007, 81: 10804-10814. 10.1128/JVI.00999-07PubMedPubMed CentralView Article
  16. Mungall BA, Middleton D, Crameri G, Bingham J, Halpin K, Russell G, Green D, McEachern J, Pritchard LI, Eaton BT, et al.: Feline model of acute Nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine. J Virol 2006, 80: 12293-12302. 10.1128/JVI.01619-06PubMedPubMed CentralView Article
  17. Graham BS, Crowe JE: Immunization against viral diseases. In Fields Virology. Edited by: Knipe DM, Griffin DE, Lamb RA, Straus SE, Howley PM, Martin MA, Roizman B. Philadelphia: Lippincott Williams & Wilkins; 2007:487-538.
  18. Wolinsky JS, Waxham MN, Server AC: Protective effects of glycoprotein-specific monoclonal antibodies on the course of experimental mumps virus meningoencephalitis. J Virol 1985, 53: 727-734.PubMedPubMed Central
  19. Plotkin SA: Vaccination against the major infectious diseases. C R Acad Sci III 1999, 322: 943-951. 10.1016/S0764-4469(00)87191-7PubMedView Article
  20. McEachern JA, Bingham J, Crameri G, Green DJ, Hancock TJ, Middleton D, Feng YR, Broder CC, Wang LF, Bossart KN: A recombinant subunit vaccine formulation protects against lethal Nipah virus challenge in cats. Vaccine 2008, 26: 3842-3852. 10.1016/j.vaccine.2008.05.016PubMedView Article
  21. Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, Geisbert JB, Feng YR, Chan YP, Hickey AC, et al.: A Hendra virus G glycoprotein subunit vaccine protects African green monkeys from Nipah virus challenge. Sci Transl Med 2012, 4: 146ra107. 10.1126/scitranslmed.3004241PubMedPubMed Central
  22. Pallister J, Middleton D, Wang LF, Klein R, Haining J, Robinson R, Yamada M, White J, Payne J, Feng YR, et al.: A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge. Vaccine 2011, 29: 5623-5630. 10.1016/j.vaccine.2011.06.015PubMedPubMed CentralView Article
  23. Bossart KN, Zhu Z, Middleton D, Klippel J, Crameri G, Bingham J, McEachern JA, Green D, Hancock TJ, Chan YP, et al.: A neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute Nipah virus infection. PLoS Pathog 2009, 5: e1000642. 10.1371/journal.ppat.1000642PubMedPubMed CentralView Article
  24. Murray K, Selleck P, Hooper P, Hyatt A, Gould A, Gleeson L, Westbury H, Hiley L, Selvey L, Rodwell B, et al.: A morbillivirus that caused fatal disease in horses and humans. Science 1995, 268: 94-97. 10.1126/science.7701348PubMedView Article
  25. Wang LF, Yu M, Hansson E, Pritchard LI, Shiell B, Michalski WP, Eaton BT: The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae. J Virol 2000, 74: 9972-9979. 10.1128/JVI.74.21.9972-9979.2000PubMedPubMed CentralView Article
  26. Mayo MA: A summary of taxonomic changes recently approved by ICTV. Arch Virol 2002, 147: 1655-1663. 10.1007/s007050200039PubMedView Article
  27. Luby SP, Gurley ES: Epidemiology of henipavirus disease in humans. Curr Top Microbiol Immunol 2012, 359: 25-40. 10.1007/82_2012_207PubMed
  28. Bossart KN, Geisbert TW, Feldmann H, Zhu Z, Feldmann F, Geisbert JB, Yan L, Feng YR, Brining D, Scott D, et al.: A neutralizing human monoclonal antibody protects african green monkeys from hendra virus challenge. Sci Transl Med 2011, 3: 105ra103. 10.1126/scitranslmed.3002901PubMedPubMed Central
  29. O’Sullivan JD, Allworth AM, Paterson DL, Snow TM, Boots R, Gleeson LJ, Gould AR, Hyatt AD, Bradfield J: Fatal encephalitis due to novel paramyxovirus transmitted from horses. Lancet 1997, 349: 93-95. 10.1016/S0140-6736(96)06162-4PubMedView Article
  30. Goh KJ, Tan CT, Chew NK, Tan PS, Kamarulzaman A, Sarji SA, Wong KT, Abdullah BJ, Chua KB, Lam SK: Clinical features of Nipah virus encephalitis among pig farmers in Malaysia. N Engl J Med 2000, 342: 1229-1235. 10.1056/NEJM200004273421701PubMedView Article
  31. Tan CT, Goh KJ, Wong KT, Sarji SA, Chua KB, Chew NK, Murugasu P, Loh YL, Chong HT, Tan KS, et al.: Relapsed and late-onset Nipah encephalitis. Ann Neurol 2002, 51: 703-708. 10.1002/ana.10212PubMedView Article
  32. Dups J, Middleton D, Yamada M, Monaghan P, Long F, Robinson R, Marsh GA, Wang LF: A new model for hendra virus encephalitis in the mouse. PLoS One 2012, 7: e40308. 10.1371/journal.pone.0040308PubMedPubMed CentralView Article
  33. Weingartl H, Czub S, Copps J, Berhane Y, Middleton D, Marszal P, Gren J, Smith G, Ganske S, Manning L, Czub M: Invasion of the central nervous system in a porcine host by Nipah virus. J Virol 2005, 79: 7528-7534. 10.1128/JVI.79.12.7528-7534.2005PubMedPubMed CentralView Article
  34. Harcourt BH, Lowe L, Tamin A, Liu X, Bankamp B, Bowden N, Rollin PE, Comer JA, Ksiazek TG, Hossain MJ, et al.: Genetic characterization of Nipah virus, Bangladesh, 2004. Emerg Infect Dis 2005, 11: 1594-1597. 10.3201/eid1110.050513PubMedPubMed CentralView Article
  35. ICDDRB: Nipah virus encephalitis outbreak over a wide area of western Bangladesh, 2004. Health and Science Bulletin 2004, 2: 7-11.
  36. Middleton DJ, Westbury HA, Morrissy CJ, van der Heide BM, Russell GM, Braun MA, Hyatt AD: Experimental Nipah virus infection in pigs and cats. J Comp Pathol 2002, 126: 124-136. 10.1053/jcpa.2001.0532PubMedView Article
Metadata
Title
Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides protection against Nipah virus disease for over 12 months
Authors
Jackie A Pallister
Reuben Klein
Rachel Arkinstall
Jessica Haining
Fenella Long
John R White
Jean Payne
Yan-Ru Feng
Lin-Fa Wang
Christopher C Broder
Deborah Middleton
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2013
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-10-237

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