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.

Design i-210 comprised a circularly permutated domain III monomer (F 1 residues 146-306 connected to F 2 residues 50-106 by a GGSGG linker), which was connected at the C-terminus of F 2 by a GGSGGSG linker to a bacteriophage T4 foldon trimerization domain (Fig 1C) . In addition to DS-Cav1 mutations, three hydrophobic surface residues were replaced by hydrophilic residues (S2 Fig). Design i-447 was also a circularly permutated domain III monomer (F 1 residues 146-306 connected to F 2 residues 51-105 by a GGPG linker) (Fig 1C) . However, in this case the trimerization domain was a computationally derived triple helical coiled coil referred to as MTQ [40] that was directly connected to the N-terminus of the domain III F 1 polypeptide without a linker. Three mutations from DS-Cav1 (S190F, S155C and S290C) were included for stability.