Fig. 6. Immunogenicity and protective efficacy of RSV preF-Δfoldon.
a–d, Balb/c mice were immunized at week 0 and week 4 with formulation buffer (Mock, n = 3) or with AS01E-adjuvanted preF or preF-Δfoldon protein (see Supplementary Fig. 7 for preF designs) at indicated doses (n = 6 per group). Two weeks after the second immunization, preF-binding antibody titres (a), foldon-binding antibody titres (b) and RSV-A CL57–FFL VNT (c) were measured in all mice; VNTs against RSV-A 18-001989 and RSV-B 17-058221 were measured in the highest dose groups and mock animals (d). Black bars represent the mean response of each group, and dotted lines refer to the LLOD or lower limit of qualification (LLOQ). All measurements under the LLOD and LLOQ were set at the LLOD and LLOQ, respectively. e,f, To assess protective efficacy, Balb/c mice (n = 3 per group) were immunized with the indicated doses of AS01B-adjuvanted preF or preF-Δfoldon protein or mock control at week 0 and week 4 and intranasally challenged at day 49 with RSV CL57–FFL. Luciferase expression was measured in the nose (e) and lungs (f) before the challenge (day 0) and on days 3, 4, 5, 6, 7 and 10 after the challenge. Means and standard deviations are indicated. The background is indicated with a dotted line. g, Luciferase expression within the animals on day 5. h,i, Immunogenicity of RSV preF-Δfoldon in pre-exposed Balb/c mice. Mice were immunized with unadjuvanted preF or preF-Δfoldon 20 weeks after pre-exposure (n = 7 per group) or were mock immunized (n = 5). Naive mice (n = 3) were added as controls. Serum samples were isolated 6 weeks after immunization. PreF-binding antibody titres (h) and RSV-A CL57–FFL VNT (i) were determined. j,k, Cynomolgus macaques (n = 4) with pre-existing immunity were immunized with 50 µg RSV-A preF-Δfoldon. PreF-binding antibody titres (j) and RSV-A CL57–FFL VNT (k) were determined in serum isolated at the indicated time points. Mean titres (log2 for VNT and log10 binding IgG titres) with standard deviation are plotted. No LOD and LLOQ are defined. Statistical testing (two sided) was performed across doses using a Tobit model (a–d) or a Tobit model with Dunnett correction for multiple comparisons (h,i).