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.

Antigenic site Ø, located at the apex of the pre-F trimer, is recognized by potent neutralizing antibodies including D25, AM22 and 5C4 [9, 13, 14] . Antigenic site II, located towards the middle of the pre-F trimer (Fig 1B) , is the binding site for antibodies palivizumab and motavizumab [9, 12, 38, 39] , which are reported to be 10-100 fold less potent than site Ø-directed antibodies [16] . Antigenic sites I and IV, which are also recognized by antibodies with lower potency, are located on the RSV F stalk region [8, 9] , and the epitopes for quaternary-specific antibodies, AM14 and MPE8, straddle both the head and stalk regions [10, 11] .