Fig. 5.

Mapping of antibody specificities induced by the ConM SOSIP.v7 trimer in rabbits. a Enzyme-linked immunosorbent assay-based competition assay measuring the interference of rabbit sera with the binding of known broadly neutralizing antibodies (bNAbs) to the ConM SOSIP.v7 trimer. The numbers represent the residual bNAb binding (0–25% in red; 26–50% in orange; 51–75% in yellow; 76–100% in green) after pre-incubation of the ConM SOSIP trimer with a 1:100 dilution of the rabbit sera. The recorded values are average values from four independent experiments. b Correlation between serum competition with PGT128 and serum competition with PG9 and VRC26.25 as determined in Fig. 5a. The Spearman r and p values of the correlations are given. A complete Spearman correlation matrix is shown in Supplementary Fig. 8. c Normalized residual binding of 3BC315 and 35O22 to ConM SOSIP.v7 trimer after adding sera of ConM SOSIP.v7 and ConM SOSIP.v7-ferritin immunized rabbits. Data are derived from Fig. 5a. Differences were determined by two-tailed Mann–Whitney U test; ***p < 0.001. d ConM NAb responses in week 22 sera from rabbits immunized with ConM SOSIP.v7 trimer (5 animals) or ConM SOSIP.v7-ferritin nanoparticle (5 animals) compared to historic control sera (week 22) from rabbits that were immunized with BG505 SOSIP.v6 (5 animals; animal ID: 1829–1833)⁵. Neutralization activity was assessed against BG505, SF162, and ConM viruses. Open symbols indicate when the autologous virus was tested. A two-tailed Mann–Whitney U test was used to compare differences; *p < 0.05; ***p < 0.001. e Neutralization titers against ConM in the presence or absence of ConM SOSIP.v7 D368R or a ConM SOSIP.v7 D368R in which the V1V2 was swapped for that of BG505. Statistical analysis was performed using the Wilcoxon matched-pairs signed-rank test. **p < 0.01. f Conformational epitopes in the V2–V3 region of ConM SOSIP.v7 that elicit strong NAbs. Residues within the apex and N332_V3 conformational epitopes are colored in blue (K169, Y173, N301, and G324) and red (Asn160 and Asn332) with glycans represented by stick models. Interfaces that are recognized by bNAbs PG9 and PGT128 are marked with dotted lines in magenta and orange, respectively. Neutralization curves of one rabbit serum (#1811, Supplementary Table 7) against key mutant viruses on the right. Bottom: alignment comparing the V1V2 amino acid sequences of ConM SOSIP.v7 with that of the ConM, ConS, TV1.21, and BG505 viruses