DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS).

Rebecca Brocato, Matthew Josleyn, John Ballantyne, Pablo Vial, Jay W Hooper
Author Information
  1. Rebecca Brocato: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.

Abstract

Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35-40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural "despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥ 5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the first report demonstrating the in vivo efficacy of any antiviral product produced using DNA vaccine-duck/egg system.

References

  1. J Immunol. 1967 Apr;98(4):820-6 [PMID: 4164559]
  2. Nat Biotechnol. 2002 Feb;20(2):114 [PMID: 11821846]
  3. Vaccine. 2008 Apr 16;26(17):2073-80 [PMID: 18375022]
  4. J Virol. 2007 Jul;81(14):7449-62 [PMID: 17475651]
  5. Immunol Today. 1995 Aug;16(8):392-8 [PMID: 7546196]
  6. J Clin Microbiol. 2000 Aug;38(8):3029-35 [PMID: 10921972]
  7. Virology. 1998 Feb 15;241(2):323-30 [PMID: 9499807]
  8. PLoS One. 2010 Apr 13;5(4):e10152 [PMID: 20405007]
  9. J Virol. 2008 Feb;82(3):1332-8 [PMID: 18032485]
  10. Lancet. 1984 Aug 4;2(8397):255-6 [PMID: 6146809]
  11. J Virol. 2003 Sep;77(18):9894-905 [PMID: 12941899]
  12. Dev Comp Immunol. 2004 Jun;28(7-8):665-72 [PMID: 15043937]
  13. J Virol. 2000 May;74(10):4908-11 [PMID: 10775634]
  14. J Allergy Clin Immunol. 1995 Apr;95(4):922 [PMID: 7722179]
  15. Virology. 1999 Mar 15;255(2):269-78 [PMID: 10069952]
  16. PLoS Pathog. 2011 Dec;7(12):e1002426 [PMID: 22194683]
  17. Lancet. 1979 Dec 8;2(8154):1216-7 [PMID: 92624]
  18. Emerg Infect Dis. 2010 Dec;16(12):1853-60 [PMID: 21122213]
  19. Toxicon. 2008 Aug 1;52(2):293-301 [PMID: 18621073]
  20. Virology. 2001 Oct 10;289(1):6-14 [PMID: 11601912]
  21. Emerg Infect Dis. 2006 Aug;12(8):1271-3 [PMID: 16965713]
  22. Vaccine. 2006 May 22;24(21):4615-7 [PMID: 16198457]
  23. Virology. 2006 Dec 5-20;356(1-2):45-9 [PMID: 16950493]
  24. Emerg Infect Dis. 2005 Dec;11(12):1848-53 [PMID: 16485469]
  25. Emerg Infect Dis. 2009 Apr;15(4):561-7 [PMID: 19331732]
  26. Toxicon. 2008 Aug 1;52(2):221-7 [PMID: 18590753]
  27. J Virol. 2001 Sep;75(18):8469-77 [PMID: 11507192]
  28. J Virol. 2009 Jul;83(14):7285-95 [PMID: 19403663]
  29. Am J Trop Med Hyg. 2000 Jun;62(6):714-7 [PMID: 11304061]
  30. Dev Comp Immunol. 2006;30(1-2):93-100 [PMID: 16150486]
  31. Clin Toxicol (Phila). 2008 Jul;46(6):539-44 [PMID: 18584367]
  32. Liver Transpl. 2007 May;13(5):647-50 [PMID: 17377915]
  33. Pediatr Infect Dis J. 2004 Oct;23(10):974-5 [PMID: 15602208]
  34. Allergy. 1995 Jul;50(7):604-9 [PMID: 8588696]
  35. Vaccine. 2000 Jul 15;18(27):3091-6 [PMID: 10856788]
  36. J Clin Virol. 2005 Dec;34 Suppl 1:S70-4 [PMID: 16461227]

Grants

  1. U01 AI045452/NIAID NIH HHS
  2. U01AI045452/NIAID NIH HHS

MeSH Term

Animals
Antibodies, Neutralizing
Antibodies, Viral
Biological Availability
Cricetinae
Dose-Response Relationship, Immunologic
Ducks
Female
Orthohantavirus
Hantavirus Pulmonary Syndrome
Humans
Immunization, Passive
Immunoglobulin G
Mesocricetus
Neutralization Tests
Plasma
Titrimetry
Vaccines, DNA

Chemicals

Antibodies, Neutralizing
Antibodies, Viral
Immunoglobulin G
Vaccines, DNA

Word Cloud

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