Experimental Vaccine Shows Fast and Long-Lasting Protection Against Crimean-Congo Hemorrhagic Fever

Crimean-Congo hemorrhagic fever, or CCHF, is one of those viruses that public-health experts worry about but most people rarely hear discussed. It spreads through tick bites and through contact with infected livestock, and it is known for its sudden onset of high fever, internal bleeding, organ failure, and a fatality rate that can reach 40%. The virus affects regions across Africa, Asia, Eastern Europe, and the Middle East, and despite decades of effort, there are still no approved vaccines or treatments available for humans.

A new study published in npj Vaccines introduces a genuinely promising development. Researchers from multiple institutions, including biomedical scientist Scott Pegan from the University of California, Riverside, have created an experimental vaccine that uses a virus-like replicon particle (VRP)—a harmless version of the virus—to trigger immunity. The latest findings show that this vaccine not only protects quickly but also offers surprisingly long-lasting immunity in mice.

How This Experimental Vaccine Works

The vaccine is engineered using a virus-like replicon particle, which resembles the actual CCHF virus in structure and cell-entry behavior but lacks the genetic material required for replication. This means it can’t cause infection while still presenting viral components to the immune system in a way that mimics real exposure.

Instead of focusing on the virus’s outer surface proteins—which is the standard design strategy for many vaccines—the team targeted an internal viral protein, specifically the N protein, also known as nucleoprotein. This protein is normally hidden inside the virus and plays a crucial role in maintaining the viral genome. What makes it especially useful for vaccine design is that it is highly conserved across different strains of CCHF, meaning it varies far less than surface proteins.

Earlier research from the same group had already shown that this vaccine can start offering protection in as little as three days after a single dose. That’s unusually fast for any vaccine and a major advantage during outbreaks, especially in remote or resource-limited areas.

What the New Study Found

The newest study focuses on the duration of immunity. Mice were given either one dose or two doses of the vaccine, and researchers monitored the strength and persistence of antibody responses over time.

Key findings include:

• Detectable antibodies remained present for up to 18 months after vaccination. For mice, this is roughly equivalent to several years of immunity in humans.
• For the first nine months, antibody levels were similar whether the mice received one dose or two.
• Mice that did receive a booster developed stronger and more stable antibodies, which translated into better and longer-lasting protection.
• The vaccine’s ability to trigger a rapid immune response appears to be linked to the body’s recognition of the internal N protein, which the immune system typically sees only during active infection.

Importantly, the replicon particle enters cells and expresses viral proteins just enough to wake up the immune system, but because it cannot replicate, there is no risk of infection.

Why Traditional CCHF Vaccine Strategies Have Struggled

CCHF has presented major difficulties for vaccine developers. Its surface glycoproteins—common targets for neutralizing antibodies—vary widely between strains. This makes it hard to design a vaccine that works broadly across the virus’s geographic range.

By focusing on internal proteins, this experimental vaccine avoids the strain-variation issue altogether. These internal proteins, especially the N protein, remain very similar across all known CCHFV strains.

Another challenge is the rapid progress of the disease. Since symptoms appear quickly after infection, a vaccine that takes weeks to become effective isn’t ideal for outbreak control. That is why the fast onset of protection shown by this VRP vaccine is so important.

What Happens Next in Vaccine Development

For any experimental vaccine to reach human testing, it must be produced under strict manufacturing standards. The research team is now working toward Good Manufacturing Practice (GMP) production. This ensures consistency, purity, and safety at a scale suitable for clinical trials.

Once GMP batches are produced, the next steps include:

• Initial safety trials in humans (Phase 1)
• Assessing immune responses in people
• Testing for broader protection across various CCHFV strains
• Ensuring the vaccine is practical for use in the countries where CCHF is endemic

The hope is that a single dose could provide meaningful protection, with a booster extending immunity even further—a vital feature for regions where repeat health-care visits can be difficult.

A Quick Overview of Crimean-Congo Hemorrhagic Fever

To give readers additional context, here are some useful details about the virus itself.

Global Distribution

CCHFV is endemic in more than 30 countries, primarily in:

• Sub-Saharan Africa
• The Middle East
• Central and Western Asia
• The Balkans and parts of Eastern Europe

Ticks from the Hyalomma genus are the main carriers, and they transmit the virus to both animals and humans. Outbreaks often arise in agricultural settings where people work closely with livestock.

Symptoms and Severity

After a short incubation period, CCHF typically begins with:

• Sudden high fever
• Fatigue and muscle aches
• Dizziness and nausea

As the infection worsens, patients may experience:

• Liver enlargement
• Severe bruising
• Bleeding from the gums, nose, or internal organs

The disease can progress rapidly, and without supportive medical care, it may lead to death within two weeks of symptom onset.

Why A Vaccine Is So Urgently Needed

Because the virus is spread by ticks and through animal handling, preventing infection purely through behavior and environmental control is extremely challenging. Healthcare workers are also at risk from patient blood or bodily fluids.

A vaccine that works quickly, lasts long, and is easy to administer could make a dramatic difference for:

• Farmers and livestock handlers
• Veterinarians
• Butchers and slaughterhouse workers
• Healthcare workers in outbreak zones
• Communities in endemic regions

The Broader Potential of Replicon Particle Vaccines

The team behind this work believes that their VRP platform could also be adapted for other dangerous pathogens. Researchers at the Centers for Disease Control and Prevention (CDC) are reportedly already testing similar prototypes for viruses like Nipah, another high-risk zoonotic virus with epidemic potential.

Because VRP-based vaccines offer both safety and strong immune activation, they may become useful candidates for multiple emerging infectious threats.

Overall Takeaway

This experimental CCHF vaccine stands out for two reasons: speed and durability. A single dose can trigger immune protection within days, and antibody responses can last more than a year and a half in mice. With a booster, the protection becomes even stronger and more stable.

While human trials are still ahead, these results provide some of the most encouraging progress yet toward a practical vaccine against one of the world’s most dangerous tick-borne diseases.

Research Paper:
Durable Humoral Immunity and Long-Term Protection Induced by a Crimean-Congo Hemorrhagic Fever Virus Replicon Particle Vaccine in Mice
https://www.nature.com/articles/s41541-025-01293-9