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

Abstract

West Nile virus (WNV), an important global human pathogen, targets neurons to cause lethal encephalitis, primarily in elderly and immunocompromised patients. Currently, there are no approved therapeutic agents or vaccines to treat WNV encephalitis. Recent studies have suggested that inflammation is a major contributor to WNV encephalitis morbidity. In this study we evaluated the use of IVIG (intravenous immunoglobulins -a clinical product comprising pooled human IgG) as an anti-inflammatory treatment in a model of lethal WNV infection. We report here that IVIG and pooled human WNV convalescent sera (WNV-IVIG) inhibited development of lethal WNV encephalitis by suppressing central nervous system (CNS) infiltration by CD45 high leukocytes. Pathogenic Ly6C high CD11b + monocytes were the major infiltrating subset in the CNS of infected control mice, whereas IVIG profoundly reduced infiltration of these pathogenic Ly6C high monocytes into the CNS of infected mice. Interestingly, WNV-IVIG was more efficacious than IVIG in controlling CNS inflammation when mice were challenged with a high-dose inoculum (10 5 versus 10 4 p.f.u.) of WNV. Importantly, adsorption of WNV E-glycoprotein neutralizing antibodies did not abrogate IVIG protection, consistent with virus neutralization not being essential for IVIG protection. These findings confirmed the potent immunomodulatory activity of generic IVIG, and emphasized its potential as an effective immunotherapeutic drug for encephalitis and other virus induced inflammatory diseases.

Fc receptors in antibody‐dependent enhancement of viral infections

“…Recently, Srivastava et al . shed insight into the mechanism underlying IVIG efficacy in animal models, identifying that IVIG preparations containing antibodies against WNV are capable of dampening inflammatory monocyte (Ly6c high CD11b + ) infiltration into the central nervous system, hence limiting the extent of inflammation and prolonging survival in a WNV mouse model. Consistent with this, recent studies by Getts et al .…”

Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?

“…IVIg plays an important role in the prevention of infectious episodes in primary immunodeficient patients, and the beneficial effects of these antibodies in the treatment of infectious diseases goes beyond simple neutralization of microorganisms or their toxins. Anti-inflammatory pathways are also critical for protection against infection [25].…”

64. Acute flaccid paralysis by Enterovirus D68 infection: First Italian description on adult patient and role of electrophysiology

“…IVIg treatment was also used for type 3 vaccine-derived poliovirus infection in an immunodeficient Iranian child (40), though to little avail. By contrast, IVIg has proved effective in West Nile virus infections (41)(42)(43)(44)(45).…”