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Establishing Immune Memory to Rabies in the CNS
Article

Establishing Immune Memory to Rabies in the CNS

Establishing Immune Memory to Rabies in the CNS
Article

Establishing Immune Memory to Rabies in the CNS

This micrograph depicts the histopathologic changes associated with rabies encephalitis prepared using an H&E stain. Note the perivascular cuffing due to the perivascular accumulation of inflammatory cell infiltrates, i.e. lymphocytes and polymorphonuclear leukocytes. Credit: CDC/Dr. Daniel P. Perl [Public domain]
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Researchers from Philadelphia University and Thomas Jefferson University have highlighted how building a strong immune memory response to rabies virus in the brain and spinal cord is key to protecting the CNS against infection.


Rabies

The rabies virus belongs to the Lyssavirus genus and transmission of the virus to humans predominantly occurs through the bite of infected dogs. All mammals are believed to be susceptible to the virus, but children in poorer rural communities are disproportionately affected by the disease. 


Rabies is, currently, 100% fatal when it enters the nervous system.


Effective prophylactic vaccine strategies are available. These prophylactic vaccines combined with control programs have resulted in the elimination of dog-mediated rabies from Western Europe, Canada, USA, and Japan.


If bitten by a dog with suspected rabies infection, post-exposure prophylaxis methods need to be administered immediately to prevent viral infection. These constitute extensive washing of the wound, a course of WHO-approved vaccines, and administration of rabies immunoglobulin.


Although effective, these vaccination methods are not easily acquired in the poorer rural communities that need them the most.


Vaccinating in Jaw Muscles

In a recent paper published in the Journal of NeuroVirology researchers from the Department of Cancer Biology and the Department of Neurological Surgery at Jefferson vaccinated mice against rabies in the jaw muscle. The reasoning behind vaccinating in the jaw muscle was that an immune response and immune memory to the virus would be developed immediately in the CNS, rather than inducing a general immune response in the blood. General immune protection is not strong or immediate enough to prevent the virus from crossing the blood-brain barrier and invading the CNS.


Through vaccinating mice in the jaw muscle the researchers found that protection against subsequent intranasal exposure to the virus was significantly improved. A ‘recall response’ or immune memory was established in the CNS of these mice which allowed for a more efficient and substantial response to the virus.


The paper states that: “Protection is significantly better in mice that have cleared attenuated virus from the CNS and is associated with a more robust CNS recall response evidently due to the presence in CNS tissues of elevated numbers of lymphocytes. ”


Craig Hooper, Professor of Cancer Biology at the Sidney Kimmel Cancer Center and co-author of the paper, explains that “Changing the location of the vaccination was enough to help develop immune memory in the CNS, where it could effectively protect against rabies in a way current vaccines can’t.”


Implications for Brain Cancer Vaccine Development

Not only has this research lead to further understanding of the CNS response to viral infection and highlighted methods that can be developed to build a stronger immune response, but it has also given insight into how the immune system fights tumors in the CNS. Establishing a strong immune response to a pathogenic or cancerous threat in the blood and peripheral tissues may not be strong enough to protect the CNS entirely. 


As Craig Hooper concludes; “This work suggests that immunity established in the blood may not be enough to fight cancer in the brain, which is useful information for developing effective vaccines against brain cancer.” 


Reference: Garcia SA, Lebrun A, Kean RB, Craig Hooper D. 2018. Clearance of attenuated rabies virus from brain tissues is required for long-term protection against CNS challenge with a pathogenic variant. Journal of Neurovirology 24(5), 606–615. doi: 10.1007/s13365-018-0655-z


Read more here: https://www.jefferson.edu/university/news/2019/02/14/battle-fought-in-the-brain.html

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