Rabies - Is There a Cure?

By: Kayley Seedath Edited by: Bindy

Namibia, South Africa

Rabies Vaccination Tracker in action — The mobile phone-based Rabies Vaccination Tracker (RVT) tool being used to capture vaccination data.

The deadliest virus in the world, formally known as rabies, is one of the oldest viruses that has a 99.9% fatality rate. Claiming the lives of over 59,000 people per year, rabies is one of the most feared viruses because it goes undetected in the body, and only shows signs when it reaches the nervous system, but by then it is too late. There have been multiple attempts to try and stop this virus in both animals and humans via vaccine, however, after you are in the last stage there is nothing that can be done to help you.... or so we think.

For over 4000 years, rabies has terrorized various animals and humans, making them exhibit aggressive-animalistic behavior when contracted. Many attempts were made to kill this virus for good, in 1885, Dr. Louis Pasteur took it upon himself to create a vaccine to help a young boy who had gotten bitten by a rabid dog. However, that variant of the vaccine only took him so far. In today’s world, the variant of the rabies phosphoprotein has only gotten more aggressive and discreet in the human body to detect. To understand where we are in current advancements, we first need to understand what rabies is and how it affects the nervous system.

Rabies is commonly transmitted by the infected saliva of animals by biting another animal or person. The location of the bite also matters, closer to your brain is considered one of the worst places to get bitten as it allows the virus to spread to the brain quicker and increase the risk of death. Rabies is a neurotropic virus that primarily affects neural tissue and neural cells. When you get bitten by a stray rabid animal and the virus enters the body, it slowly starts to replicate itself. However, due to its slower activity in the muscle tissue, the immune system doesn’t detect it until it reaches the nervous system. That's when it reaches the blood barrier of the brain, which then is a sign that it is too late. When it gets into the brain it replicates and messes with the brain’s cellular proteins which causes neuro dysfunction. Signs that the virus has settled into the body include excessive anxiety, agitation, confusion, hyperactivity, difficulty swallowing, excessive salivation, hydrophobia ( fear of water ), insomnia, and partial paralysis. After the virus has settled in, it travels back into the body and vital organs, primarily the salivary glands in the mouth to be then further transmitted. Hypersalivation ensures that there is enough rabies-infected saliva, the hydrophobia aspect and trouble swallowing ensures that it stays there. Hence, if you see that an animal is foaming at the mouth and acting rapidly, move away because they most likely have rabies and are looking for where to spread their poison next.

So far there are only two types of vaccines to protect against rabies: nerve tissue and cell culture vaccines. The WHO recommends replacing the nerve tissue vaccines with the more safe and effective vaccines developed through cell culture as soon as possible. The main types of cell culture vaccines, pre-exposure, are called the Imovax Rabies, RabAvert, and rabies immune globulin (RIG) can prevent rabies before you are exposed/infected. This vaccine helps lower the risk of symptoms if you may have been exposed to rabies. However, if you are infected before getting the vaccine, it may not be effective at all.

These vaccines pose threats to humans and domestic animals. For humans, some side effects include soreness, excessive itching, headaches, nausea, abdominal pain & dizziness. Additionally, rabies vaccines are currently made from killed virus. However, this inactivation process can alter the vaccine molecules and introduce the wrong form of the rabies virus to the immune system. Another downside is that current rabies vaccination programs for dogs rely on the use of injectable shots. This method for protecting dogs from rabies in low-income countries can be tricky since many dogs have not been to a veterinarian and may not be accustomed to close interactions with people. This then causes an important question to arise, “ Is there a cure for rabies after you have contracted the virus?” As it stands, In recent years, more and more information has accumulated on the structure and functions of rabies phosphoprotein (P). It has been shown that it is involved in the induction of innate immunity by promoting interferon production. Some groups are targeting P for genetic alteration and creating effective live attenuated vaccines for animal use. New studies show that an oral rabies vaccine for animals can help solve this issue. The ONRAB oral vaccine bait was developed in Ontario. It underwent a significant safety review before it was licensed for use in wildlife in 2013. This oral vaccine is most effective for fox and raccoon strain rabies control. Animals are immunized against rabies about two weeks after they chew the rabies vaccine bait. However, most rabies cases, in humans, are by dog/bat bites so how would this benefit human cases?

A new study published in EMBO Molecular Medicine suggests that a new single-dose monoclonal antibody therapy might be able to treat symptomatic rabies in humans. The study’s authors, Dr. Brain Schaefer and Dr. Christopher Broder are professors in the Uniformed Services University of the Health Sciences (USU) Department of Microbiology and Immunology. Their study demonstrated the effectiveness of an anti-lyssavirus human monoclonal antibody as a treatment for animals whose central nervous systems were already infected with lyssavirus. The treated animal subjects survived the usually fatal infection. A monoclonal antibody injected into lab mice successfully protected them from a lethal dose of rabies virus, researchers reported in a World Rabies Day article.

The researchers designed the antibody to block the rabies virus and prevent its spread. They were surprised to find that a single dose of the antibody effectively reversed the rabies infection even after it had reached the nervous system, preventing death. This antibody appears to spur the immune system to create smaller immune cells that can pass through the blood-brain barrier and into the nervous system, where they effectively target and destroy rabies virus, the findings show. This potential cure for advanced rabies is particularly promising because it could be distributed easily to places that need it, Schaffner said. Monoclonal antibodies can be produced fairly readily now and could be widely distributed around the world,” he said. “We could treat those cases, and they're 100% fatal now. Once this disease gets established, there are only a literal handful of cases that have been treated and have survived rabies.”

By introducing the Monoclonal vaccine, the accessibility and effectiveness of rabies prevention could be significantly improved, particularly in remote or underserved areas. This advancement not only offers hope for reducing the incidence of rabies but also underscores the importance of innovation in public health initiatives. Ultimately, the development and deployment of the Monoclonal vaccine and the oral animal vaccines represent a promising step toward a world free from the threat of this deadly disease.

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