“If this research works in humans, this is Nobel Prize-worthy. And I would be honored to see Rick win that prize,” said Andrew J. Geall, PhD, the Vice President of Formulations & Chemistry at Avidity Biosciences.
Geall, originally with Novartis Vaccines, funded the research of Professor Richard Bucala at the Yale School of Medicine. Under Bucala’s leadership, his team of scientists created a vaccine that fights malaria in mouse models and protects against reinfection.
Malaria is the second most prevalent cause of infectious disease, with 300-600 million people affected each year. The disease leads to over one million deaths each year, affecting mostly children under the age of five. Malaria is a parasitic infection transmitted by the bite of mosquitoes. Symptoms are flu-like, including chills, fever, and sweating, but when left untreated, may result in death. Currently, antibiotics are the only preventative medicine approach that has shown any effect. No vaccine is available yet.
Utilizing an RNA vaccine and technology that Geall had worked on at Novartis, Bucala and his team trained mouse immune systems to recognize a specific malaria-associated protein, plasmodiummacrophage migration inhibitory factor (PMIF), and elicit a response. RNA vaccines provide the body with instructions to create proteins that work to achieve protective immunity against a foreign invader. In malaria, the PMIF protein suppresses memory T cells, the disease-fighting cells in the immune system that respond to pathogens and protect the body against a second infection. Without these T cells, the immune system is inequipped to combat the disease. Inhibition of PMIF-mediated suppression could therefore prevent immune evasion and allow the body to mount a response.
With Geall’s RNA-based vaccine, a strain of the malaria parasite lacking PMIF was injected in the muscle cells of mice. The mice consequently secreted an altered version of the PMIF protein, which spurred the immune system into action.
“Now, the immune system is seeing all these foreign proteins and detecting them,” Geall said.
The mice developed “sterile immunity,” a term describing the phenomenon that once the immune system has a memory of a foreign parasite, it is well-equipped to deal with the pathogen upon reinfection. The mice no longer suffer from the disease, as they have developed immunity. This is very difficult to achieve: similarly to HIV, the malaria parasite has the ability to avoid detection by the host and consequently remain under the radar. As a result, targeting the parasite with conventional vaccines has shown little success.
The beauty of the RNA-based approach is that it is very simple to make and highly cost-effective. “The scale is so small compared to a traditional production facility. It is a potential solution for very costly vaccine production in 10 to 15 years time,” Geall added. Whereas traditional vaccines take around 6 months to be made, RNA based vaccines can be manufactured in a third of the time at lower production costs. This is precisely why RNA-based vaccines are more effective in treating pandemics with pathogens that evolve rapidly.
Going forward, Geall and Bucala hope to test their vaccine in clinical trials, with the goal of reproducing their results in humans. Currently, they are corresponding with funding agencies to get the vaccine tested in the clinic. Both Geall and Bucala will be involved in the next steps. Geall recognizes the importance of bringing this vaccine to market quickly, as 40 percent of the world’s population lives in malaria-risk areas, especially in Sub-Saharan Africa.
“This is the most exciting piece of research we have ever done,” Geall said.