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


CONCLUSIONS
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.
Ben-Nathan
David
D
The Shraga Segal Dept. of Microbiology and Immunology, Ben Gurion University, Beer Sheva, Israel. davidbn@013.net.il
Gershoni-Yahalom
Orly
O
Samina
Itzchak
I
Khinich
Yevgeny
Y
Nur
Israel
I
Laub
Orgad
O
Gottreich
Ahuva
A
Simanov
Michael
M
Porgador
Angel
A
Rager-Zisman
Bracha
B
Orr
Nadav
N
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000627:therapeutic use; D001782:Blood Donors; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007557:Israel / Q000453:epidemiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014709:Vero Cells; D014901:West Nile Fever / Q000188:drug therapy* / Q000453:epidemiology; D014902:West Nile virus / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous