Replicating RNA Vaccine For Crimean-Congo Hemorrhagic Fever Virus

Crimean-Congo hemorrhagic fever (CCHF) is a deadly hemorrhagic fever having a high mortality rate. The disease results from infection of an individual by Crimean-Congo hemorrhagic fever virus (CCHFV), which is a tick-borne bunyavirus endemic in Southern and Eastern Europe, Africa, the Middle East, and Asia. Geographically, case distribution is consistent with the range of Hyalomma genus ticks, the main reservoir of CCHFV, and is likely to expand due to climate change. Humans may be infected from tick bites, through contact with infected animals or animal tissue. Nosocomial human-to-human transmission has also been described primarily for healthcare workers. Initial symptoms of CCHF include acute onset of a non-specific febrile illness consisting of sudden fever, myalgia, diarrhea, nausea, and vomiting. The hemorrhagic phase is characterized by large areas of severe bruising and uncontrolled bleeding throughout the body; among hospitalized patients, case fatality rates have ranged from 9-50%. Currently, there is no approved specific antiviral or vaccine for CCHFV infection.

Scientists at NIAID in collaboration with HDT Bio have developed a replicating RNA (repRNA) vaccine based on Venezuelan Equine Encephalitis Virus replicon RNA expressing either the nucleoprotein (repNP) or the glycoprotein precursor (repGPC) from CCHFV alone or in combination.  In mice, the repNP vaccine primarily elicited a robust but non-neutralizing antibody response while repGPC elicited primarily cellular immunity against epitopes in the CCHFV NSm and Gc proteins. Vaccination with repNP or repNP + repGPC resulted in protection against challenge with a heterologous strain of CCHFV in mice.