Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus

Boyington, Jeffrey C.; Joyce, M. Gordon; Sastry, Mallika; Stewart-Jones, Guillaume B. E.; Chen, Man; Kong, Wing-Pui; Ngwuta, Joan O.; Thomas, Paul V.; Tsybovsky, Yaroslav; Yang, Yongping; Zhang, Baoshan; Chen, Lei; Druz, Aliaksandr; Georgiev, Ivelin S.; Ko, Kiyoon; Zhou, Tongqing; Mascola, John R.; Graham, Barney S.; Kwong, Peter D.

The two immunogens (i-273 and i-210) that elicited the lowest titers of RSV neutralization (geometric means of 2 and 9, respectively) had low micromolar affinity to the antigenic site IIdirected antibody motavizumab, whereas i-693 and i-447 which induce substantially higher titers bound motavizumab at nanomolar affinities. This suggests that antigenic site II may potentially play a role in the overall effectiveness of the head-only immunogens, which is consistent with the neutralization competition data (Fig 5B) . The small size and extensive surface mutagenesis of the i-273 monomer, and the greater structural heterogeneity and surface mutations of the i-210 trimer relative to i-447 may also have diminished the capabilities of these head-only immunogens.