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.

It remains to be seen how many of the head-only immunogens are viable vaccine candidates. Results from the "best" four immunogens, nonetheless, already demonstrate the ability of head-only RSV F immunogens to boost to high titers previously elicited RSV-neutralizing responses to the RSV F glycoprotein. Together, these results indicate the head-only immunogens, i-693 and i-447, to be particularly suited to boosting RSV F-specific antibody responses in the setting of pre-existing immunity-a result of particular significance for maternal immunization and for vaccine protection of the elderly. The left panel shows a ribbon diagram of domain III consisting of polypeptides F 1 (green) and F 2 (blue). Antigenic site Ø and site II are red and orange respectively. The middle and right panels depict two separate ways to reconnect F 1 and F 2 into a single chain through the addition of linkers (dotted lines). A cartoon of the genetic construct is shown above each ribbon diagram depicting the topology of the F 1 (green) and F 2 (blue) polypeptides.