FIG. 4.

Cross-protection induced by live attenuated vaccine strains. (A) Survival rates of C57BL/6 mice immunized with 4cps in a single dose (▪; n = 12) versus two doses (▴; n = 12), compared to the vehicle-only control (•; n = 15), following intranasal challenge with the type 6A isolate. Statistical differences compared to the vehicle control were determined by the Kaplan-Meier log-rank test. (B) Colonization density at day 9 postinoculation of mice challenged with the type 4 parent isolate (solid bars) or type 6A parent isolate (hatched bars) after immunization with the indicated live vaccine of the other serotype. One dose of the vaccine strain was administered except where a second dose is indicated (2×). Values represent the means of 6 to 12 mice/group ± the standard errors of the means. The dotted line indicates the limit of detection. Colonization density was analyzed in surviving mice. Eight mice in the mock-immunized group and four animals in the 4cps single-dose group that did not survive were not included in the analysis. Statistical differences were determined using the Mann-Whitney test with comparisons to the corresponding mock-immunized group. *, P < 0.0278; **, P = 0.0028.