lCm Low-dose (106 PFU) animalarrows indicate mild multifocal mixed mononuclear and polymorphonuclear cell infiltration (l??10) and minimal granulomatous inflammation, i.e., foreign body granuloma (m??40). the scheduled termination, 49?days post the first dosing (recovery animal). There was no similar finding on the right hind limb Afzelin (which was injected at the same occasion, with the same dose and volume). This may be attributed to inadvertent injection of the sciatic nerve which can result in lameness; however, histopathological evaluation performed 49?days post the first dosing revealed Afzelin no potential treatment-related lesions in the sciatic nerve, brain or spinal cord. No additional clinical signs were evident in any of the animals throughout the entire study period. No local reactions at the injection site area were observed in any of the animals throughout the entire study period. An increase in mean group body weight was evident in all groups throughout the study period and no statistically significant difference was noted in mean group body weight gain at the end of the study period between the vaccine-treated groups vs. the control group. A statistically significant increase in the mean group body temperature vs. the control group, within the normal body temperature range of rabbits, was noted in both vaccine-treated groups (females) on the first dosing session and the low-dose-treated group (males) a day following the first dosing (Table S3). Body temperature higher than the normal range of rabbits (i.e.,??39.8?C, according to the US and European pharmacopeias) was measured in both vaccines-treated groups but also in the control group of both sexes on the day of the second injection, Day 14 (40.37?C, 40.03?C, Afzelin and 40.18?C in low-dose, high-dose and control females; 39.84?C, 39.71?C, and 40.14?C in low-dose, high-dose and control males, respectively) and, therefore, were not considered be to related to the tested vaccine. No such changes were observed on Day 28, following the third injection. Food consumption values were within the normal range throughout the study period. All animals exhibited normal appearance of blood vessels and the optic disc during indirect ophthalmoscopy examinations. There were no marked differences in urinalysis values of the animals assigned to the treated groups vs. the control group. Clinical Rabbit Polyclonal to NCBP1 pathology Mean group values of most parameters in both vaccine-treated groups were comparable to those of the control group, within each sex. A few statistically significant differences were found; however, these findings can Afzelin be considered incidental since the values were within the normal range of reference values and/or similar to baseline values. A statistically significant increase in mean fibrinogen level was noted in the low-dose males (374.8?mg/dl) vs. controls (275?mg/dl), 31?days post the first dosing. A similar increase was noted in low-dose females (366.8?mg/dl vs. 297?mg/dl in controls) and in high-dose males (375.5?mg/dl vs. 275?mg/dl in controls); however, these were not statistically Afzelin significant. Elevation in fibrinogen level is expected following vaccine injection and is generally consistent with immune stimulation and inflammation. A significant increase in mean fibrinogen, an acute phase protein, was noted 3?days post-dosing in the high-dose male group (329?mg/dl vs. 275?mg/dl in controls); however, this increase was mainly attributed to the single male which bore less weight on its left hind limb following injection. No similar increases in fibrinogen levels were noted on day 3 in either low-dose males or in low- and high-dose females. In all cases, the fibrinogen level returned to baseline values on 49?days post-first dosing. C-reactive protein (CRP) Group mean values of CRP of both the low- and high-dose- treated groups (males and females) were similar to that of the control group at the various time points and were in the range of expected normal values (0.2-2?ng/ml). No dose response was observed at any specific time point, indicating no systemic inflammation response. Antibody levels All vaccine-injected rabbits responded to the vaccine by induction of SARS-CoV-2 neutralizing antibodies and spike-specific binding antibodies. A gradual increase in neutralizing and binding antibody titers at both vaccine doses was noted during vaccination (Fig.?1a, b). The evaluated response kinetics of both antibody types was comparable, and a significant increase of around one log was observed from Day 13 to Day 41. A neutralizing response to the primary vaccination was detected (Day 13) in 40% of the animals vaccinated with the low dose and 80% of the animals vaccinated with the high dose. The initial binding response was detected in 10% of the low dose and 90% in the high dose. Following boost (Day 27), all animals responded, as demonstrated by a.