A/SLOV15 S13 gave superior LAIV shedding and serum immune responses and enhanced protection from wt challenge in ferrets.

Groups of 4 ferrets were vaccinated with 4.0 Log₁₀ FFU of monovalent V1 (MLAIV-V1), monovalent S13 (MLAIV-S13), V1 in a representative 2017–18 quadrivalent formulation (QLAIV-V1) and S13 in the same representative quadrivalent formulation (QLAIV-S13). Four unvaccinated ferrets were also included as controls. (A) Schematic of 31-day optimised ferret efficacy study plan. Days are along the horizontal axis with major interventions shown by the black arrows, coloured boxes indicating sampling points and grey arrow showing hourly core body temperature readings. (B) LAIV shedding was measured by TCID₅₀ using nasal swab samples that were collected daily days 1–5 post vaccination. A/SLOV15 V1 and A/SLOV15 S13 shedding were compared by a paired t-test. (C) Serum immune responses were measured by HAI using antisera collected 21 days post-vaccination. MLAIV-V1, QLAIV-V1, MLAIV-S13 and QLAIV-S13 were compared to the unvaccinated control animals by performing a Kruskal-Wallis test followed by Dunn’s multiple comparisons test. (D) wt shedding was measured by TCID₅₀ using nasal swab samples that were collected daily between days 1–3 post wt challenge and the geometric mean of wt shedding per day for each ferret depicted by the scatter plot. Shedding of vaccinated animals relative to unvaccinated animals was compared by a Kruskal-Wallis test followed by Dunn’s multiple comparison test. (E) Ferret core body temperature was measured hourly from pre-vaccination to study termination. Fever values as a measure of influenza-like illness for individual ferrets were obtained by subtracting temperature values recorded post-wt challenge from baseline temperature for each animal. Each vaccinated group was compared to the unvaccinated control group by one-way ANOVA followed by Dunnet’s multiple comparisons test. Mean values for individual animals are depicted by the scatter plots (C-E), mean values for all animals in each vaccination group are indicated by the columns (C-E), error bars show standard deviation (B,E) or median with 95% CI (C,D), and the dotted lines represent the lower limit of detection for each assay (B-D). Values below the LLD are plotted as ½ LLD for statistical purposes. P values are indicated as follows: **** P<0.0001, *** P<0.001, ** P<0.01 and * P<0.05 (B-E).