A new single-dose monoclonal antibody therapy reversed signs of active rabies infections in mice
The single-does treatment prevented fatalities even though the virus had entered the central nervous system
A new study published in EMBO Molecular Medicine suggested 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.
Current treatments for lyssavirus include vaccines and immediate post-exposure treatments. Immediate post-exposure treatment involves a series of injections given several days apart. No interventions are available once the virus reaches the nervous system and begins causing neurological symptoms. This is why urgent treatment is essential after a human is bitten or scratched by an infected animal. An infection with the lyssavirus is nearly always fatal for humans once it begins to cause the symptomatic condition of rabies.
Rabies is rare, and most transmission to humans comes from encounters with wild dogs. Areas where these encounters are more common also tend to have limited access to medical care. This can make receiving multiple treatment injections in a series challenging. The study’s authors say a single-dose monoclonal antibody treatment could simplify rabies care for those who need it.
“Given that the vast majority of human rabies occurs in rural areas of the developing world with limited healthcare resources, we would argue that a single-dose, easily administered therapy is a much more viable approach for human therapy than a treatment that requires highly invasive, continuous infusion to the CNS,” they stated.
Previous research found that a lab-created monoclonal antibody, F11, can effectively block lyssavirus infections in lab cultures. This new study, led by researchers Dr. Kate Mastraccio and Celeste Huaman, a PhD candidate in the USU Emerging Infectious Diseases Graduate Program, aimed to see if F11 could stop a lyssavirus infection before it became rabies. The study used two strains of the lyssavirus.
F11 and similar antiviral monoclonal antibodies work by neutralizing viruses. They’re able to bind to the virus and prevent further infection of cells. However, in past usage, they haven’t been able to neutralize viruses that have infected the central nervous system because they are not able to cross the blood-brain barrier.
Based on this knowledge, researchers expected F11 to block lyssavirus at the early stages before it entered and replicated in the spinal cord and brain. They were surprised to discover that F11 was also effective at later stages. In the study, F11 was able to reverse signs of neurological infection even after they were present and was able to prevent death even after lyssavirus entered the central nervous system.
Low virus levels remained after a single treatment with the F11 antibody. However, they did not replicate and increase, and signs and symptoms of infection did not return. This suggests that a single dose of F11 could effectively treat humans with symptomatic rabies. Additionally, it’s possible that these findings could be applied to other viruses that target the spinal cord and brain and could lead to new treatments for conditions that affect the central nervous system.
More research and testing on a larger scale are still needed, but this potential single-dose treatment could be big news for treating this global health concern.
The long search for rabies treatment
Louis Pasteur administered the first human rabies vaccine, created from homogenates found in the spinal cord of an infected rabbit, in 1885. However, searching for a rabies treatment significantly predates the late 19th century. Rabies cases are documented as far back in human history as 600–1,000 BCE, and the condition has always been fatal once symptoms appeared.
Treatments for rabies have remained elusive. Since 1970, an estimated 3 million people worldwide have developed symptomatic rabies. Only about 30 of them have survived, and most of those 30 survivors were left with severe neurological damage.
Since treatment for symptomatic rabies has been challenging, efforts to combat the infection have largely focused on prevention. This has included efforts to prevent transmission from dogs and other animals to humans and efforts to prevent the lyssavirus from reaching the central nervous system. Rabies vaccines for dogs have been a crucial step in reducing transmission.
Additional efforts, such as recommended pre-exposure vaccines for people who might come in contact with the virus and post-exposure prophylaxis (PEP), also help control the virus. About 15 million people receive a post-bite PEP treatment annually. The World Health Organization (WHO) estimates that this saves “hundreds of thousands” of lives each year.
However, it is difficult to get a true estimate of global numbers, as most rabies fatalities occur in areas with limited access to medical care and are likely under-reported. The WHO estimates that 95% of all rabies deaths occur in Africa and Asia. A course of PEP treatment requires multiple injections on a 14-day schedule and costs about $40 USD in Africa and $49 USD in Asia; in many areas with the highest risk of rabies, the average daily income per person is about $1-2 USD a day.