Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies
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SHORT COMMUNICATION
Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies Washington C. Agostinho 1
&
Paulo E. Brandão 1
Received: 21 January 2020 / Revised: 1 May 2020 / Accepted: 14 July 2020 # Journal of NeuroVirology, Inc. 2020
Abstract Rabies is a neurological disease with 100% lethality. Some of the rare human patients who survived after multiple drug treatment had severe sequelae. The present study showed that after 48 h of RABV inoculation, mice injected intracerebrally with antiRABV F (ab’)2 plus Bioporter® showed 70% survival compared to the control group, suggesting that transfection of anti-RABV antibodies to the brain may prevent or delay the spread of RABV at an early stage of infection. This result may provide important protocol results in intracellular antibody delivery to prevent the fatal outcome of the disease. Keywords Rabies . Antibodies . Transfection . Therapy
Introduction Rabies is a zoonotic neurological disease with 100% lethality; some of the few human patients who survived after a multidrug treatment developed severe motor impairment due to ischemic encephalopathy followed by necrosis of the hippocampus, cerebellum, and cortex (Burton et al. 2005; Manoj et al. 2016). The use of immunomodulators and antivirals has not been shown to be effective in inhibiting the progression of the disease when tested in mice and humans (van Thiel et al. 2009; Marosi et al. 2018). Circa 59,000 human deaths occur worldwide yearly due to rabies, and although it is preventable with pre and post-exposure prophylaxis, the logistics and costs involved in rabies treatments are a limiting factor to saving lives (Hampson et al. 2015). Rabies lyssavirus RABV (Mononegavirales:Rhabdoviridae: Lyssavirus) is a neurotropic virus with a circa 11 kb negativesense single-stranded RNA as a genome that codes for the nucleoprotein (N), phosphoprotein (P), matrix protein (M), envelope glycoprotein (G), and the RNA-dependent RNAWashington C. Agostinho and Paulo E. Brandão contributed equally to this work. * Washington C. Agostinho [email protected] 1
Department of Preventive Veterinary Medicine and Animal Health, School of Veterinary Medicine, University of São Paulo, São Paulo, Brazil
polymerase L protein (Jackson and Wunner 2007), and it is most often transmitted amongst mammals via saliva after an initial local replication in muscle cells that follows to the central nervous system (CNS) via axons (Lewis et al. 2000). Within a variable period of time after infection, signs of hyperactivity, hypersalivation and hydrophobia are detectable. The virus causes enough damage to the brain in a few days that the infection invariably leads to coma and death by cardio-respiratory arrest (WHO 2013). Here, we show that the use of intracerebral transfection of anti-RABV antibodies to treat mice inoculated with RABV reduces mortality and extends the incubation period of rabies.
Results Probing the transfection to mouse brains with Bioporter® complexed with an FITC-antibody control protein (Genlantis)
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