Fig. 6: Cross-reactive antibodies elicited by reoH2HA recognize group 2 HA-stem.
a, A three-dose immunization study with H2 HA or reoH2HA adjuvanted with a higher dose of CpG with alum in BLAB/c mice. b, Serum stem-specific IgG titers over time (n = 10 mice per group). Arrows indicate prime and boost immunizations in b. c, Cross-reactive binding of group 1 (H1 NC/99, H1 CA/09 and H5 VT/04) and group 2 (H3 VC/75, H7 NT/27 and H7 SH/13) HAs by week 7 antisera. Each circle represents a single mouse (n = 10 mice per group). Dashed lines indicate the limit of quantification in b,c. Data are presented as geometric mean ± s.d. of the log10‐transformed values (b,c). Comparison of two groups was performed using the two-tailed Mann–Whitney U-test. P values of 0.05 or less were considered significant. d,e, nsEMPEM analyses for week 12 (d) or week 7 (e) pooled antisera raised against H2 HA (top row) or reoH2HA (bottom row). Composite maps generated from negative-stain reconstructions of polyclonal immune complexes with H2 HA, H7 HA or H3 HA are shown for each group. Representative 2D class averages with the polyclonal Fab labeled are shown for immune complexes in low abundance, in which dotted lines highlight the likely position for the Fab population.
