Crimean-Congo hemorrhagic fever (CCHF) is one of the world’s most dangerous yet overlooked infectious diseases. Spread by ticks and livestock, the virus causes sudden fever, organ failure, and internal bleeding, killing up to 40% of those infected. Outbreaks have been reported across parts of Africa, Asia, Eastern Europe, and the Middle East. Despite decades of research, no approved vaccines or treatments exist.
Now, a mouse study, published in the journal npj Vaccines, brings fresh optimism. A research team, including biomedical scientist Scott Pegan at the University of California, Riverside, has developed a vaccine made from a non-infectious version of the CCHF virus that protects quickly and provides long-lasting immunity.
Previous research by the team had shown that this experimental vaccine could protect animals within just three days after a single dose — unusually fast for any vaccine. The new study now reports that the protection is durable as well.
The researchers tested how long the immune response lasted in mice after one or two doses. They found that antibodies remained detectable for up to 18 months — roughly equivalent to several years in humans. Antibody levels were similar between the one- and two-dose groups for about nine months, but animals that received a booster developed stronger, more stable antibodies that offered better and longer-lasting protection.
According to Pegan, creating a vaccine for CCHF has been notoriously difficult.
“CCHF is one of those viruses where you can’t simply use the outer coat proteins to make a vaccine,” said Pegan, a professor of biomedical sciences in the UCR School of Medicine.
Instead, the team took a different route. Their vaccine uses what’s known as a virus-like replicon particle — something that looks and behaves like the real virus but is completely harmless.
“Made in the lab, this particle can enter cells like a normal virus, but it doesn’t have the genetic material to replicate,” Pegan said. “That allows the immune system to respond to the virus-like particle without any risk of infection.”
What makes this vaccine stand out is the part of the CCHF virus it targets, Pegan explained. He said most vaccines train the immune system to recognize proteins on the virus’s surface, but this one focuses on internal proteins — particularly a component called the N protein.
“Our earlier work showed that the N protein, which is usually hidden inside the virus, turns out to be the key to protective immunity,” he said.
This unconventional strategy also explains why the vaccine works so quickly, Pegan said.
“We were amazed to see antibodies appear within just a few days,” he added. “The rapid response is one reason this platform is succeeding where others haven’t.”
The new findings on long-term protection add to the growing promise of the CCHF vaccine. A single dose appears strong enough for meaningful protection, while a booster helps keep immunity steady for even longer.
“That could be crucial for outbreak regions where people might not have easy access to follow-up vaccinations,” Pegan said.
Next, the research team plans to move toward large-scale production under Good Manufacturing Practice (GMP) standards, a key step before human clinical trials can begin.
“We can make the vaccine in the lab right now, but GMP ensures it can be produced safely, consistently, and at scale,” Pegan said.
Beyond CCHF, the same technology could help tackle other dangerous viruses.
“Our partners at the Centers for Disease Control and Prevention are already exploring this platform for diseases like Nipah virus,” Pegan said. “It’s a flexible system that could be adapted for a range of emerging pathogens.”
Ultimately, the team believes this vaccine could make a difference — especially for communities and health workers in regions where CCHF is endemic.
“Having something that can protect quickly and last a long time could save lives and change how we respond to outbreaks,” Pegan said.
Pegan was joined in the study by scientists at the Centers for Disease Control and Prevention (CDC), U.S. Department of Agriculture, and Auburn University in Alabama.
The research was supported in part by the CDC and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The findings and conclusions do not necessarily represent the official position of the CDC.
The title of the paper is “Durable humoral immunity and long-term protection induced by a Crimean-Congo hemorrhagic fever virus replicon particle vaccine in mice.”
Header image credit: Md Babul Hosen, iStock / Getty Images Plus.
