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.

Our results demonstrate that a head-only RSV F immunogen boost can both focus and enhance the elicited response to antigenic sites associated with the RSV F head. The reduced size and increased thermostability of the head-only immunogens described here may also have advantages in terms of both expression and manufacturing. In addition to mammalian cell culture, these small immunogens may also be amenable to less expensive plant [43, 44] or bacterial-based expression systems [45, 46] as well as yeast [47, 48] or insect cell culture [49, 50] . Indeed, full length RSV F protein has been successfully expressed in apples [51] , tomatoes [52] , and insect cells [53] . Furthermore, the successful use of live chimeric vectors such as Sendai [54] or human parainfluenza virus type 3 [55] or replication-defective vectors such as adenovirus [56, 57] or Modified Vaccinia Ankara [57] to express RSV F protein and elicit immune responses in vector-immunized animals suggests alternative delivery methods could also be applied to head-only RSV F immunogens in a vaccination setting.