Dual-Antigen CCHFV Vaccine Induces Neutralizing Immunity and Protection Against Lethal Challenge

Crab-Congo hemorrhagic fever virus (CCHFV) poses a significant threat due to its high mortality rate and widespread distribution. Developing a vaccine for CCHFV has proven difficult, as scientists struggle to find antigens that stimulate both cellular and humoral immunity. Previous research demonstrated that the CCHF nucleoprotein (NP) does induce protective responses in mice and non-human primates, but it does not generate neutralizing antibodies.

To address this issue, researchers systematically screened six chimeric DNA vaccines that included various CCHF glycoproteins in combination with NP. A specific construct consisting of the ectodomain of the glycoprotein Gc and NP emerged as the most effective. This Gc-NP gene was then developed into an mRNA vaccine using a scalable manufacturing process.

The Gc-NP mRNA-LNP vaccine produced strong antibody and T-cell responses, similar to those generated by the DNA vaccine, even at a lower dosage. Both vaccine methods generated neutralizing antibodies against CCHFV pseudovirus and provided protection against both CCHFV strains, Hoti and IbAr10200, in mice. This study highlights the importance of comprehensive antigen screening and the utilization of genetic vaccine platforms in the development of a highly effective multi-antigen CCHFV vaccine.