Researchers from Thomas Jefferson University and the University of Maryland Baltimore, in collaboration with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) and the Geneva Foundation, have developed a promising new vaccine candidate that protects against Lassa fever. The study, published in npj Vaccines on August 9, 2024, demonstrated that the vaccine effectively prevents severe cases of the disease and death in preclinical animal models and paves the way for research in people.
To date, several Lassa candidate vaccines are currently in development. However, out of these, Matthias Schnell, PhD, director of the Jefferson Center for Vaccines and Pandemic Preparedness at Thomas Jefferson University, who co-led the study, pointed out that his team's LASSARAB vaccine has an advantage. He noted that the two other platforms in development for Lassa fever are both based on live viral vectors, "which come with their own safety issues," he says. "Our vaccine is a deactivated or killed vaccine which is considered safer in general."
The vaccine, named LASSARAB, uses a deactivated rabies virus platform to deliver antigens to protect against the Lassa fever virus. Lassa fever is a severe hemorrhagic disease that is endemic to parts of West Africa, causing an estimated 300,000 to 500,000 infections and over 5,000 deaths each year. The disease can lead to severe complications including organ failure, deafness, and long-term neurological disorders. Currently, there are no licensed vaccines to prevent Lassa fever.
"The damage to a patient is devastating," says Kathleen Cashman, PhD, a virologist and principal investigator at The Geneva Foundation supporting USAMRIID who also co-led the study. She adds that the virus infects and compromises cells, causing multiple organ failures which can be fatal. "It is a very severe disease that's difficult to protect against, so when you find something that can keep you from dying, that's pretty astounding."
The researchers used 12 young non-human primates to test the vaccine, half receiving two doses of the LASSARAB vaccine, and the other half receiving CORAVAX, a COVID-19 vaccine, as a negative control. While both used rabies as a vector, the antigens used to activate an immune response were different. Over 28 days, the control group exhibited more severe disease symptoms, greater damage to their internal organs, and did not survive, while the LASSARAB-vaccinated group had less damage and survived until the end of the study. The researchers also noted that much remains unknown about the persistence of the disease in young animals in general, highlighting the need for further research.
While the vaccine protected against severe disease and death and reduced fever, it did not prevent infection. The researchers believe the 28-day study period was not long enough to fully assess the vaccine's ability to provide long-term immunity. They are optimistic that longer-term studies with more mature animal models will provide further insights into the vaccine's ability to prevent long-term side effects.
The rabies platform used in the LASSARAB vaccine was developed by Dr. Schnell's lab and offers several key advantages. In addition to protecting against Lassa fever, the vaccine also protects against rabies which is an important consideration for many Lassa-endemic regions. Previous studies have shown that a similar rabies-based vaccine against the Ebola virus can also remain stable at a variety of temperatures including 50 degrees Celsius for up to two weeks. Dr. Schnell, also chair of the Department of Microbiology and Immunology at Sidney Kimmel Medical College, highlighted that rabies vaccines have a proven safety profile, allowing for their use in children and immunosuppressed populations. This dual protection could be particularly beneficial in regions where both diseases are prevalent.
"If you get vaccinated and boosted against rabies, most people have lifelong protection," Dr. Schnell says. "So, we hope that the protection against Lassa will also be long-lived, which is important."
Funding for this study was provided by a $30 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), which has been crucial in advancing the vaccine candidate to this critical stage. "This kind of work needs government and nonprofit funding," says Dr. Schnell, who added that the team is very grateful to receive this funding since there are limited commercial incentives from pharmaceutical companies for this type of vaccine. "This is not a SARS-CoV-2 vaccine. This vaccine is for neglected infectious diseases in a region of poor financial standing, so these people need our help."
To that end, Dr. Schnell's Lassa virus vaccine is now headed to a phase 1 clinical trial in November after successfully completing an Investigational New Drug (IND) application with the Food and Drug Administration.
Author disclosures and other supplementary materials are available at nature.com.
Article reference: Gabrielle Scher, Catherine Yankowski, Drishya Kurup, Nicole M. Josleyn, Eric R. Wilkinson, Jay Wells, Jesse Steffens, Ginger Lynn, Sean Vantongeren, Xiankun Zeng, Nancy Twenhafel, Kathleen A. Cashman & Matthias J. Schnell, "Inactivated rabies-based Lassa fever virus vaccine candidate LASSARAB protects nonhuman primates from lethal disease," npj Vaccines, DOI: 10.1038/s41541-024-00930-z, 2024.
