Fig. 1.
Vaccine safety studies in mice. Survival and average body temperature of wild type and immunodeficient mice vaccinated with live-attenuated chimeric alphavirus vaccine (SIN/ZPC). Panels A and B show the survival and average body temperature of parental C57BL/6 (wild type, WT) and immunodeficient mice inoculated with live-attenuated chimeric alphavirus vaccine (SIN/ZPC). Panel C shows the average body temperature following VEEV infection of unvaccinated mice. The total percentage of surviving mice (A) and the average body temperature (B) of SIN/ZPC vaccinated IFNγR KO, γδ TCR KO, μMT KO and WT mice before and after vaccination on day 0 were evaluated, as follows. Vaccination: eleven to 18-week-old, female mice were inoculated on day 0 and day 34 subcutaneously into the medial thigh with the chimeric SIN/ZPC virus at a dose of 5 × 105 plaque forming units in a total volume of 100 μl. Mock-vaccinated mice (indicated as “WT* unvacc”) were inoculated subcutaneously with 100 μl of PBS. Virus challenge: SIN/ZPC or mock-vaccinated mice were inoculated on day 0 intranasally with an identical dose of virulent VEEV (ZPC738) in 40 μl of PBS and deaths were recorded. Daily telemetric monitoring of body temperature was performed for a total period of 14 days, beginning 2 days prior to the first vaccination on day 0. Asterisk (⁎) indicates parental C57BL/6 mice (wild type, WT). The characteristics of the parental WT and immunodeficient mice are described in Materials and methods (Table 1). (C) Positive control for telemetric monitoring. The body temperature of unvaccinated γδ TCR KO mice 2 days before (day − 1 and − 2) and 7 days after (day + 1 through + 7) infection with virulent VEEV (ZPC738) on day 0.