Fig. 5: Evolution of HA2 position 32 influences the antigenicity of the lower stem epitope.
A Occurrence of different amino acid variants at HA2 position 32 of human H3N2 strains from 1968 to the present was analyzed based on 33,000 human H3N2 HA sequences from the GSAID database65. The x-axis represents the years, while the y-axis shows the percentage of strains containing a particular amino acid at HA2 position 32 in a given year. Thr, Ile, and Arg are represented by orange, brown, and green lines, respectively. B The structures of AG2-G02 binding to HA stem with I32HA2 and R32HA2 are modeled. The binding affinity (Kd) of AG2-G02 Fab to different HA stem variants is indicated in parentheses. C–E The binding of plasma samples from (C) pre-2003 adults (n = 20), (D) post-2011 adults (n = 20), and (E) post-2011 infants (n = 15) to H3 stem with either T32HA2, I32HA2 or R32HA2 is measured by ELISA. The y-axis represents the area under the curve (AUC) of four serial 10-fold dilutions of serum (1:100, 1:1,000, 1:10,000, and 1:100,000). P-values were determined using a paired two-tailed Student’s t-test.
