Log10means of fold change in ELISA titers for each type of immunization at the indicated days. Each circle represents the log10mean fold change in ED50titers from mice against a single viral strain of sera from mice that were immunized with the specified immunogen (solid circles = matched; open circles = mismatched; colors for different strains defined in A). The mean of mean titers is compared in (C) and (E) by Tukeys multiple comparison test with the Geisser-Greenhouse correction calculated using GraphPad Prism, with pairings by viral strain. Error bars associated with each data point are standard deviations. Significant differences between immunized groups linked by horizontal lines are indicated by asterisks:*p <0.05,**p <0.01,***p <0.001,****p <0.0001. Binding responses at day 0 (before NP or other vaccine immunizations) showed significant differences across cohorts in titers elicited by the pre-vaccinations.43To account for different mean responses at day 0 between cohorts, we applied baseline corrections (seeSTAR Methods). Uncorrected binding data for (B) and (C) are shown inFigures S4B and S4C.