Prophylactic and Therapeutic Efficacy of Human Intravenous Immunoglobulin in Treating West Nile Virus Infection in Mice

Abstract

West Nile virus (WNV) is a mosquito-borne disease found most commonly in Africa, West Asia, and the Middle East, where up to 40% of the human population possesses antibodies. It is an emerging disease in the United States. Humans infected with WNV develop a febrile illness that can progress to meningitis or encephalitis. In mice, WNV causes central nervous system infection, paralysis, encephalitis, and death. Currently, no specific therapy or vaccine has been approved for human use. We examined the prophylactic and therapeutic efficacy of pooled human plasma (PP) and intravenous immunoglobulin (IVIG) for treatment of WNV-infected mice. Full protection was achieved when the infected mice were treated with pooled plasma or IVIG obtained from healthy Israeli blood donors that contained WNV-specific antibodies. Similar treatments using PP or IVIG obtained from US blood donors had no protective effect. Recovery of the lethally infected mice was dependent on the dose and time of IVIG administration. These results indicate that antibodies play a major role in protection and recovery from WNV infection and that IVIG can be used as first-line therapy.

West Nile virus meningoencephalitis

“…61 Passive transfer of WNV-specific antibodies or immunoglobulin can protect mice and hamsters against WNV infection in experimental models of disease. 62,63 Antibody transfer can offer some protection to mice even after the virus has reached the CNS, although efficacy declines markedly with time after WNV infection, indicating that rapid diagnosis and timely administration are vital. Uncontrolled clinical reports describe an apparent beneficial effect in two patients given the Israeli human intravenous immunoglobulin preparation Omr-IgG-am, which contains high titers of neutralizing antibody to WNV, although a third treated patient died.…”

“…62,74 In some animal models, vaccination with Japanese encephalitis virus, 75 St Louis encephalitis virus or Kunjin virus (a subtype of WNV) confers relative protection from severe WNV infection, but two studies have shown that prior Japanese encephalitis, yellow fever or dengue virus vaccination does not induce protective neutralizing antibody responses to WNV. 76,77 Potential strategies for human WNV vaccine development include use of inactivated or attenuated WNV strains, chimeric live virus vaccines (in which WNV genes are inserted into the genetic background of another flavivirus), and recombinant-subunitbased vaccines.…”

Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis

“…Several reports have documented the success of IVIG (intravenous immunoglobulins) as a treatment for patients with WNV CNS infections (Agrawal & Petersen, 2003;Kumar et al, 2004;Makhoul et al, 2009;Morelli et al, 2010;Rhee et al, 2011;Saquib et al, 2008;Shimoni et al, 2012;Wadei et al, 2004;Yango et al, 2014). Studies in murine models using low doses of IVIG preparations that contained high titres of WNV neutralizing antibodies confirmed robust protection from WNV encephalitis (Ben-Nathan et al, 2003. Passive transfer of WNV-specific monoclonal or murine polyclonal antibodies aborted or limited WNV infections in rodent models in a dose-, time-and complementdependent manner (Agrawal & Petersen, 2003;Mehlhop et al, 2005;Morrey et al, 2006).…”

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

“…In pre-clinical studies, anti-WNV IgGs substantially reduced mortality in WNV-infected mice. In contrast, the mortality is observed in WNV-infected mice when a polyvalent is administered instead of specific IgG (Ben-Nathan et al, 2003). In light of these findings, investigation of the potential of specific human anti-dengue IgG would appear to be a reasonable proposition.…”