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Publication : Induced protection from a CCHFV-M DNA vaccine requires CD8(+) T cells.

First Author  Golden JW Year  2023
Journal  Virus Res Volume  334
Pages  199173 PubMed ID  37459918
Mgi Jnum  J:354818 Mgi Id  MGI:7715016
Doi  10.1016/j.virusres.2023.199173 Citation  Golden JW, et al. (2023) Induced protection from a CCHFV-M DNA vaccine requires CD8(+) T cells. Virus Res 334:199173
abstractText  Crimean-Congo hemorrhagic fever (CCHF) is a World Health Organization prioritized disease because its broad distribution and severity of disease make it a global health threat. Despite advancements in preclinical vaccine development for CCHF virus (CCHFV), including multiple platforms targeting multiple antigens, a clear definition of the adaptive immune correlates of protection is lacking. Levels of neutralizing antibodies in vaccinated animal models do not necessarily correlate with protection, suggesting that cellular immunity, such as CD8(+) T cells, might have an important role in protection in this model. Using a well-established IFN-I antibody blockade mouse model (IS) and a DNA-based vaccine encoding the CCHFV M-segment glycoprotein precursor, we investigated the role of humoral and T cell immunity in vaccine-mediated protection in mice genetically devoid of these immune compartments. We found that in the absence of the B-cell compartment (microMT knockout mice), protection provided by the vaccine was not reduced. In contrast, in the absence of CD8(+) T cells (CD8(+) knockout mice) the vaccine-mediated protection was significantly diminished. Importantly, humoral responses to the vaccine in CD8(+) T-cell knockout mice were equivalent to wild-type mice. These findings indicated that CD8(+) T-cell responses are necessary and sufficient to promote protection in mice vaccinated with the M-segment DNA vaccine. Identifying a crucial role of the cellular immunity to protect against CCHFV should help guide the development of CCHFV-targeting vaccines.
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