FIG 6.

Minimal protective dose and safe and effective vaccine range. (A and B) Six- to 7-week-old female C57BL/6 mice (n = 6/group) were s.c. vaccinated with the indicated low doses of FMDV A12-WT or A12-P1 deopt mutant and challenged 21 days after vaccination (dpv) with a lethal dose of FMDV A12-WT. Clinical disease was followed for 7 days after inoculation, and percent survival was calculated as (number of surviving animals/number of animals per group) · 100 daily (A). Serum samples collected during 7 days after inoculation were assayed for the presence of virus by plaque assay on BHK-21 cells (B). (C) Neutralizing Abs in sera of mice inoculated with FMDV A12-P1 deopt or A12-WT before (dpv) and after (dpc) challenge. Titers are expressed as the inverse dilution of serum yielding a 50% reduction of virus titer (log₁₀ TCID₅₀/ml). Each data point represents the mean (± SD) for each group. (D) Vaccine margin of safety for A12-P1 deopt or A12-WT virus. The left ordinate indicates the percentage of animals surviving the primary inoculation (black squares) with either virus at doses ranging between 10⁰ and 10⁷ PFU. After 21 days, the surviving, vaccinated animals were challenged with a single lethal dose of FMDV A12-WT. Survival was monitored (right ordinate; open circles) for A12-P1 deopt (top panel)- or A12-WT (bottom panel)-vaccinated mice. Gray boxes represent the margin of safety.