Filoviruses can cause some of the deadliest diseases on the planet including the Ebola, Sudan and Marburg virus diseases. According to the World Health Organization, fatality rates have varied from 25% to 90% in past outbreaks, making it crucial to find effective treatments and diagnostics to help prevent spread and deaths.
Monoclonal antibodies, which can neutralize viruses to prevent or reverse disease, may hold the key when it comes to developing these life-saving treatments.
What are monoclonal antibodies?
“Mono” means one and “clonal” means clone or copy. These antibodies are produced from B cells (cells that create antibodies) to neutralize viruses by binding tightly to the outside of them and preventing the viruses from getting into cells in our bodies.
Dr. Logan Banadyga, a research scientist at the Public Health Agency of Canada’s National Microbiology Laboratory (NML) and his team generate monoclonal antibodies for filoviruses (which cause hemorrhagic fever like Ebola, Sudan and Marburg). They do this by isolating a single B cell and amplifying it to produce lots of antibodies, which are all identical and bind to the same pathogen. Monoclonal antibodies can target the pathogen very specifically which makes them effective at preventing or treating diseases. The team also tests these antibodies against viruses in the highest level of biocontainment labs.
The NML is currently doing research to identify monoclonal antibodies that target more than one type of filovirus (many filoviruses have been identified and at least six of them are known to cause disease in humans). To do this, they need to figure out which features the filoviruses share so they can be targeted with the same monoclonal antibody, which Dr. Banadyga likens to “finding a single puzzle piece that can fit into several different puzzles.”
Ultimately, NML scientists hope to develop treatments that can neutralize filoviruses for which there are currently no approved vaccines or treatments. All these viruses are similar enough that it could be possible to identify a monoclonal antibody that recognizes more than one of them. This is important because filovirus outbreaks continue to happen, recently with the Sudan virus in Uganda and currently the Marburg virus in Equatorial Guinea and Tanzania.
“Filoviruses pose a significant threat in Africa, but they could also potentially be exported to Canada and other countries. If we can advance the development of treatments, not only will we help protect the public health of people in Africa, but we can also protect global public health,” says Dr. Banadyga.
Collaborations provide new insights
In addition to the NML’s own research, they are also teaming up with other scientists to investigate how monoclonal antibodies can help treat filoviruses. Dr. Banadyga says there is much to be gained by combining resources and expertise.
“Working with people who have different skillsets gives you new insights you wouldn’t otherwise be exposed to and helps advance research projects in a way we wouldn’t be able to do individually,” says Dr. Banadyga.
One of the major collaborations that the NML is involved in is led by Dr. Erica Ollmann Saphire at the La Jolla Institute for Immunology in San Diego and funded by the U.S. National Institutes of Health. The NML’s contribution to the project is to use monoclonal antibodies that other labs have generated from filoviruses and then evaluate them in animal models, since the NML has a great deal of experience in running these types of studies. In fact, some NML researchers are world leaders when it comes to developing animal models necessary for conducting pre-clinical research. Why is this important? Because researchers need to test novel treatments in an animal model before starting human clinical trials.
Dr. Banadyga says that establishing this partnership is a significant success, with contributions from leading scientists from different institutions around the world. “It’s an honour for us to be involved and demonstrate the value of our expertise on an international stage,” he shares.
The NML also has a partnership with the University of Guelph’s Dr. Sarah Wootton that involves using monoclonal antibodies as a preventative treatment for filoviruses, where the body is used as a “bioreactor” to produce antibodies. This involves taking the genetic sequences of monoclonal antibodies and putting it into a viral-like particle that delivers genetic information to the muscle cells of the body through an injection. The muscles read the genetic information and start producing the antibody and providing protection from disease. The benefit of this treatment is that it can produce sustained high levels of antibodies and is relatively inexpensive to produce. The NML is helping assess this method of delivery in animal models and the results are promising so far.
Additionally, the NML is working with the Canadian Food Inspection Agency (CFIA) to create test strips using antibodies that can diagnose filovirus infections. Dr. Ming Yang at the CFIA is experienced in developing strip tests, and the NML relies on her expertise to make the tests with antibodies generated by the NML. These tests, which can be done quickly and easily outside of a diagnostic laboratory by people who are not medical experts, would be valuable in in-field situations where test results are needed quickly to help contain outbreaks.
The success of these collaborations has left Dr. Banadyga feeling optimistic about future advancements in the research of treatments and vaccines for filoviruses. “We’re lucky to be part of a team of really well qualified scientists and to be part of a society that values science enough to provide the resources for us to work to cure and treat viruses. It’s a privilege to conduct scientific research,” he concluded.