Fig. 3: DH270.6 encounter state design improves the selection of target mutations.
From: Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
A Association rates for the parent CH8483 Env SOSIP (black) and CH848 DE3 design (red) for the DH270 lineage UCA, intermediates, and DH270.6. B Affinities for the parent CH8483 Env SOSIP (black) and CH848 DE3 design (red) for the DH270 lineage UCA, intermediates, and DH270.6. Log scaling is used for visual clarity. C DH270.UCA Ramos B cell BCR triggering was measured as a percentage of calcium flux relative to the maximum flux observed for an anti-IgM Fab2. D cryo-EM map of the DE3 design bound to DH270.6 (gray) and a difference map between the parent CH848 bound to DH270.6 and the DE3 design bound to DH270.6 highlighting the N442-glycan missing density (green). Contour levels 1.64 and 0.57, respectively. E Panel of pseudo-virus IC50 neutralization titers for sera from IA4 knock-in mice immunized with either the glycan hole-filled CH848-d949 SOSIP trimer (N = 12 mice in group) or the DE3 design (N = 13 mice in group). Significance was calculated using a two-tailed, non-parametric Mann-Whitney test and is marked by an asterisk (*p < 0.05; CH848.10.17, p = 0.203; CH848.10.17 Holes Filled, p = 0.320; CH848.10.17.N332T, p = 0.220; CH848.10.17.DT, p = 0.019; CH848.10.17.DT.N332T, p = 0.964; Q23, p = 0.011; JFRL, p = 0.220; TRO.11, p = 0.055; DU156.12, p > 0.999; ZM106F, p = 0.096; CAAN5342, p > 0.999; 92RW20, p = 0.264; 6101.1, p = 0.024; MLV-SVA, p > 0.999). F Mutation frequencies for the IA4 key improbable mutations heavy chain R98T and light chain L48Y. Bars indicate the geometric mean frequencies. Significance was calculated using a two-tailed, non-parametric Mann-Whitney test and is marked by an asterisk (*p < 0.05, N = 11 mice in the CH848-d949 immunized group and N = 13 mice in the DE3 immunized group). Source data are provided as a Source Data file.
