Fig. 6. Summary of endpoints demonstrates reduction in A/BOL13 efficacy in multivalent formulations relative to A/NC99.

Data from multiple endpoints for A/BOL13 a and A/NC99 b vaccine groups were expressed as heatmaps. Each panel shows a single vaccine formulation (top to bottom: monovalent, trivalent, and quadrivalent LAIV, and unvaccinated). Each row represents an individual ferret, with four animals per dose group, with vaccine doses ordered from 3.0 (top) to 6.0 log₁₀ FFU (bottom). Endpoints shown are, left to right: HAI titer; MN titer; geometric mean wt virus shedding (Days 1–3, TCID₅₀); wt virus titer in NT tissue (TCID₅₀); wt virus titer in lung tissue (RT-qPCR); fever (°C). All endpoints, irrespective of units of measurement, were normalized to a uniform 0–1 scale. Immune responses and protection equivalent to the average of the 6.0 log₁₀ FFU monovalent vaccine group were calibrated to 0 (navy blue). Immune responses and protection equivalent to average data from unvaccinated controls were calibrated to 1 (red). White cells indicate mean of red/navy blue. Gray cells indicate missing data points owing to insufficient tissue sample quantity or corrupt telemetry data. A/BOL13 A/Bolivia/559/2013, A/NC99 A/New Caledonia/20/1999, FFU fluorescent focus units, HAI hemagglutination inhibition, LRT lower respiratory tract, MN microneutralization, NT nasal turbinate, QLAIV quadrivalent LAIV, RT-qPCR quantitative reverse transcription-polymerase chain reaction, TCID₅₀ tissue culture infectious dose 50%, URT upper respiratory tract, wt wild type.