Open Access Research article

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

David Ben-Nathan12*, Orly Gershoni-Yahalom1, Itzchak Samina2, Yevgeny Khinich2, Israel Nur3, Orgad Laub3, Ahuva Gottreich4, Michael Simanov2, Angel Porgador1, Bracha Rager-Zisman1 and Nadav Orr3

Author Affiliations

1 The Shraga Segal Dept. of Microbiology and Immunology, Ben Gurion University, Beer Sheva, Israel

2 Kimron Veterinary Institute, Department of Virology, Beit Dagan, Israel

3 OMRIX Biopharmaceuticals, Weizmann Science Park, Ness-Ziona, Israel

4 MDA National Blood Services, Tel Hashomer, Kiryat Ono, Israel

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BMC Infectious Diseases 2009, 9:18  doi:10.1186/1471-2334-9-18

Published: 17 February 2009

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.