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. 2024 May 23;9:88. doi: 10.1038/s41541-024-00877-1

Fig. 4. Vaccination reduces pathology and CCHFV antigen in liver and spleen.

Fig. 4

a Mean hepatic inflammation and necrosis and splenic lymphoid reactivity scores (0–4) (error bars represent standard deviation). Mean liver inflammation and necrosis scores were reduced with vaccination 1 week or more prior to inoculation, compared to short-course (-3D) or unvaccinated controls (no VRP, given DMEM alone). Mean liver inflammation scores were similar for short-course and unvaccinated animals at both 3 and 6 days post infection (dpi), but mean liver necrosis score decreased from 3 to 6 dpi in -3D animals and increased from 3 to 6 dpi in unvaccinated animals. Consistent lymphoid reactivity was present only in -3D and unvaccinated animals and increased from 3 to 6 dpi. Individual animals are represented. Bars and error bars indicate mean ± SEM. b Liver and spleen pathology (top two rows) and CCHFV antigen detection by immunohistochemistry (bottom two rows) at 6 dpi. No or rare small foci of inflammation and hepatocyte necrosis (arrows) were present with vaccine administration 7 or more days prior to inoculation. Livers in -3D and unvaccinated animals both have prominent inflammation and necrotic hepatocytes (arrowheads). Spleens from -28D- and -14D-vaccinated animals showed non-reactive follicles, while -7D-vaccinated animals showed mild reactivity, and spleens from -3D-vaccinated and unvaccinated mice showed similar, marked lymphoid reactivity characterized by follicular expansion by lymphoblasts and prominent plasma cells (*). Immunohistochemistry for CCHFV shows immunostaining (red) of necrotic hepatocytes in -3D and unvaccinated livers; more numerous, confluent clusters of hepatocytes were stained in livers of unvaccinated animals than in short-course vaccinees. Scattered staining of histiocytes was present in a -3D spleen and more prevalent in the spleen of an unvaccinated animal. No immunostaining was seen in livers or spleens from animals vaccinated 1 week or more prior to inoculation. Original magnifications 20 ×, scale bars are 50 μM. Top two rows: hematoxylin-eosin (H&E) stain; bottom two rows: CCHF immunohistochemistry (IHC) with Fast Red chromogen.