Using high titer West Nile intravenous immunoglobulin from selected Israeli donors for treatment of West Nile virus infection

BMC Infect Dis. 2009 Feb 17:9:18. doi: 10.1186/1471-2334-9-18.

Abstract

Background: West Nile Virus (WNV) is endemic in Israel and a significant level of antibodies is present in the population due to natural exposure. Anecdotal cases suggested that the presence of anti-WNV antibodies in intravenous immunoglobulin (IVIG) from Israeli donors (IVIG-IL) assisted the recovery of patients with severe WNV infection.

Methods: To enhance the therapeutic efficacy of IVIG-IL against WNV infection, OMRIX Biopharmaceuticals, Israel, have developed a strategy for selection of plasma units from a 10% fraction of Israeli blood donors with anti-WNV antibodies. Positive units were processed into pharmaceutical grade WNV IVIG (WNIG). Following inoculation with WNV, mice received i.p. injections of different doses (0.01-8 mg/mouse) of IVIG-IL or WNIG, according to the specific experimental protocol.

Results: WNIG was about 10 times more potent (per gr of IgG) than was regular IVIG-IL when tested by ELISA and neutralization assays. In a mouse lethal WNV infection model, prophylactic treatment with WNIG was at least 5-10-fold more potent as compared to treatment with IVIG-IL. Treatment with WNIG during active encephalitis, three or four days following WNV infection, had a significant protective effect. WNIG was also very effective in protecting immunosuppressed mice. Indeed, treatment of dexamethasone-immunosuppressed mice with 0.2 or 1.0 mg WNIG 4 h after virus infection, led to 100% survival.

Conclusion: IVIG produced from selected plasma donated in WNV endemic regions can be used to produce WNV IVIG with superior activity for therapeutic and prophylactic measures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • Antibodies, Viral / therapeutic use
  • Blood Donors*
  • Chlorocebus aethiops
  • Female
  • Humans
  • Immunization, Passive*
  • Immunoglobulin G / therapeutic use
  • Immunoglobulins, Intravenous / therapeutic use*
  • Israel / epidemiology
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Vero Cells
  • West Nile Fever / drug therapy*
  • West Nile Fever / epidemiology
  • West Nile virus / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulins, Intravenous