A study in npj vaccines in May 2024 presents a “promising” replicating RNA vaccine in a rhesus macaque model of Crimean-Congo haemorrhagic fever virus (CCHFV). The tick-borne febrile illness has expanded geographically, which places an “increasing number of people” at risk of CCHFV infection. As there are “no widely available vaccines” and a treatment with “unclear efficacy”, there is a clear unmet need. The authors present their model as an alternative to the established cynomolgus macaque model and find that their vaccine is “immunogenic and protective in non-human primates after prime-boost immunisation”.
CCHF
The authors state that Crimean-Congo haemorrhagic fever, caused by CCHFV, can cause “severe haemorrhagic disease in infected humans”, beginning as a non-specific fever, myalgia, nausea, diarrhoea, and general malaise. This can “rapidly progress” and in some regions, case fatality rates can be as high as 30-40%. The current, widely-used therapy is ribavirin, but efficacy in both human and animal models is “conflicting and suggestive of poor efficacy” when administered later in infection.
While there is an inactivated preparation of CCHFV grown in mouse brains used as a vaccine in Bulgaria, there are no approved vaccines for CCHF. Thus, prevention is limited to “control of exposure”.
Research to date
Previous research evaluated a replicating RNA (repRNA) vaccine for CCHFV in a lethal mouse challenge model. The vaccine is based on an alphavirus replicon system, in which the structural proteins of the Venezuelan equine encephalitis virus are replaced with a gene-of-interest, resulting in RNA that can self-amplify. This leads to dose sparing and mimics an authentic viral infection without the ability to spread from the initially transfected cell.
The paper states that delivery of the repRNA is achieved by complexing the RNA with a cationic nanocarrier called LION with several features:
- May induce less systemic inflammation than current lipid nanoparticles
- Has been manufactured under current good manufacturing practices
- Has demonstrated safety and immunogenicity in humans
- Is the basis for a product that achieved emergency use authorisation in India
Research has established a non-human primate (NHP) model of CCHF in cynomolgus macaques. The latest paper presents an alternative model; the passaged strain of CCHFV causes viraemia and mild disease “consistently” in rhesus macaques.
Supportive data
The data demonstrate the protective efficacy of a repRNA vaccine for CCHFV in RM, with this model providing a “viable alternative model”. In the study, CCHFV-specific antibodies “significantly and inversely” correlated with viral loads in multiple tissues, including key tissues like liver, kidney, heart, and lung tissue.
“All animals developed a CCHFV-specific response following vaccination, demonstrating that our repRNA platform is immunogenic in RM.”
In both current and previous research, nucleoprotein (NP)-specific antibodies “appear to be the major correlate of protection”. While the CM vaccinated with DNA-expressed NP alone were protected from CCHFV challenge, the repRNA vaccine “may provide quicker immunity” than that approach. Furthermore, CCHFV-specific humoral immunity was observed “after a single immunisation”, but boosting may “still be warranted to confer optimal immunity”.
“Cumulatively, our data support the continued development of this vaccine for CCHFV.”
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