Clinical rabies is an incurable disease with rabies virus rapidly replicating within central nerve system of the afflicted host, inducing a series of neurological symptoms with fatal consequence. Recently we presented a proof of concept showing a strong potential to stop the advance of clinical rabies, of which a cocktail of monoclonal antibodies (RVC20 and RVC58) was delivered continuously into the brain of mice via intracerebroventricular (ICV) route at the early timepoint of clinical rabies. This treatment cleared the virus from infected brains in more than 50% of treated group, or at least delaying the endpoint of the animals. However, since the rabies-endemic countries that take up most of clinical rabies cases are developing countries in Africa and Asia, the medical and economic burden of delivering antibodies on-site through ICV route could prevent the realisation of therapy. In the current work, we tested a simpler route for administration; we deliver the cocktail of antibodies via intravenous route and observe the response of mice challenged with high dose of rabies virus. From this work, we found that a significant number of animals have survived the viral infection after receiving the cocktail treatment or have the endpoint delayed, and the human antibodies are present in their central nervous system. Even though some of neurological symptoms in infected mice were retained, survived animals showed no viral RNA or a negligible amount of it in CNS and relatively similar clinical scores to healthy control group. Mechanism of the clearance of virus from the brain seems to be related to a global and early activation of microglia, as observed in histological examination. On this sequencing project, we aim to isolate microglia from infected- and antibody-treated-mice with means of immunostaining and FACS sorting, isolate RNA and look into the differential expression of genes compared to non-treated or non-infected animals.
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