Evaluation of the efficacy of a recombinant subunit West Nile vaccine in Syrian golden hamsters

Am J Trop Med Hyg. 2008 Dec;79(6):955-62.

Abstract

The efficacy of a recombinant subunit West Nile (WN) vaccine candidate was determined in a hamster model of encephalitis. Animals included young, aged, and immunocompromised animals in an effort to simulate key groups at risk of WN virus-induced disease. Groups of aged (12 month old), weanling, and adult hamsters rendered leukopenic after immunization were immunized subcutaneously with a WN virus recombinant envelope protein (WN-80E) with or without WN virus non-structural protein 1 (NS1) mixed with adjuvant or adjuvant alone. A challenge dose of wild-type WN virus was administered to produce 40-100% mortality in the control hamsters. The recombinant antigen preparations containing WN-80E with or without WN NS1 gave similar results. Hamsters in both groups had a strong antibody response after immunization, and none of the aged or weanling animals became ill or developed detectable viremia after challenge with WN virus at 2 weeks after booster vaccination. However, mortality among the control animals (administered adjuvant without antigen) at 2 weeks after booster challenge was 40-60%. In hamsters rendered leukopenic after immunization, survival rates up to 80% were observed, and a low-level viremia was detected in the vaccinated and challenged hamsters. The survival rate was significantly (P<0.05) higher in animals vaccinated with a higher dose of WN-80E than a lower dose. The addition of NS1 did not significantly affect survival after challenge. In contrast, all of the control animals that received adjuvant only developed a very high level of viremia, and the mortality rate was 100%. These findings indicate that the recombinant WN vaccines induced antibody in and afforded protection to young and aged hamsters and immunosuppressed hamsters.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Animals
  • Cricetinae
  • Cyclophosphamide / pharmacology
  • Dose-Response Relationship, Immunologic
  • Female
  • Immunocompromised Host
  • Immunosuppressive Agents / pharmacology
  • Mesocricetus
  • Protein Subunits / immunology*
  • Recombinant Proteins / immunology*
  • Time Factors
  • Viral Vaccines / immunology*
  • Viremia
  • Weaning
  • West Nile Fever / pathology
  • West Nile Fever / prevention & control*

Substances

  • Immunosuppressive Agents
  • Protein Subunits
  • Recombinant Proteins
  • Viral Vaccines
  • Cyclophosphamide