Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

Weight status, physical activity, and vascular health in 9- to 12-year-old children.

BACKGROUND: The purpose of this study was to determine the independent and joint association of weight status and physical activity on resting blood pressure and C-reactive protein in children. METHODS: Participants were 174 (71 males, 103 females) children (mean age = 10.5 ± 0.4 yrs). Physical activity was self-reported, body mass index was calculated from measured height and body mass, and blood pressure was measured according to standard procedures. A subset of 91 children had C-reactive protein measured by fingerstick blood sample. Four weight/physical activity groups were created by cross tabulation of weight status classification and physical activity level. RESULTS: The prevalence of low physical activity (< 5 days/wk moderate-vigorous activity) did not differ between overweight and normal weight children (50%). Physical activity was not correlated with C-reactive protein (r = 0.01; P = 0.91) and C-reactive protein was not significantly different between physical activity groups (P = 0.87). Physical activity did not modify the difference in blood pressure or C-reactive protein within weight categories. CONCLUSIONS: Fatness (specifically overweight and obesity), but not physical activity, was shown to be associated with blood pressure and C-reactive protein levels in children. Physical activity did not attenuate blood pressure or C-reactive protein in overweight and obese children.

Joint association of fatness and physical activity on resting blood pressure in 5- to 9-year-old children.

The purpose of this study was to determine the joint association of fatness and physical activity on resting blood pressure in children. Subjects included 157 children (age 5.5-9.5 years). Moderate-to-vigorous physical activity (MVPA, min/day), body fatness, and resting blood pressure were measured. Four categories were created by cross tabulation of high/normal levels of fatness and high/low levels of MVPA. There were significant differences in systolic blood pressure and mean arterial pressure across the fat/MVPA groups (p < .05). Regardless of participating in an acceptable level of MVPA, overfat children had higher resting systolic blood pressure than normal fat children. MVPA did not significantly attenuate blood pressure within a fat category.