Single-dose vaccine to protect against Crimean-Congo Hemorraghic Fever virus

April 29, 2019

Research teams at the University of Georgia College of Pharmacy Department of Pharmaceutical and Biomedical Sciences, led by Associate Professor Scott Pegan, in collaboration with the CDC, led by Éric Bergeron, have successfully discovered a single-dose replicon particle vaccine that provides complete protection against the Crimean-Congo Hemorraghic Fever (CCHF) virus in mice.  Results of the study have been published in Emerging Microbes and Infections.

Since December 2015, the WHO has maintained a list of Blueprint priority diseases in an effort to accelerate the research and development of urgently needed vaccines and drugs to treat them.  Diseases on this list pose a public health risk, because they have the potential to cause major epidemics and no effective treatment or vaccine exists to combat them.

In February 2018, WHO reviewed their Blueprint for the prevention of epidemics and placed CCHF at the top of the priorities list. This tick-borne viral disease is found throughout Africa, the Balkans, the Middle East and Asia and has the potential to emerge in Western Europe as evidenced by two recent cases in Spain.

First described in Crimea in 1947 and later in the Congo in 1956, CCHF has a high fatality rate—10 to 40 percent of cases end in death. In some regions, the fatality rate is as high as 80 percent.  CCHF is acquired through bites from infected ticks of the genus Hyalomma and is also spread by contact with infected animals, such as goats and sheep, or handling infected animal tissue during slaughter. This virus can be spread from human to human in hospitals, placing medical workers at risk.  Travelers to regions where infected ticks are found may also contract CCHF.

Often occurring in remote regions, CCHF is difficult to prevent.  There is no therapeutic treatment for this disease.  Anti-viral drugs, such as ribavirin, have not proven effective as a method to treat CCHF. Previously developed CCHF vaccine approaches have required multiple dosing, which is difficult to provide during a severe outbreak.  Up until now, there has been no effective single-dose vaccine to prevent CCHF.

Not only is CCHF a threat to world health, it also poses a threat to national defense. The CCHF virus can be weaponized, and U.S. military forces are exposed to this risk in areas of strategic importance, such as Afghanistan, Iraq, and Syria. Consequently, the CCHF virus is included in Bioterrorism Category A by the CDC, along with Ebola and the Marburg virus, among other potential bioterrorism agents.

The good news is that when a state-of-the-art CCHFV mice model received the new replicon particle vaccine, they were completely protected against the CCHF virus. The vaccine not only provides complete protection with a single dose but can be handled in the lab without the biosafety risks of using live virus.  Although it closely mimics the structure of the CCHF virus, the replicon particle has been genetically altered to limit its replication to a single cycle so that it cannot proliferate and spread.

Safe and effective in mice, this promising new vaccine may help reduce the threat of CCHFV, although further study is needed to fully understand the immune response involved, determine efficacy of vaccine timing and describe the mechanism of protection.

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