Development of a stabilized trimer pre-fusion RSV F recombinant viral glycoprotein vaccine

Publication Year:
2016
Usage 87
Abstract Views 87
Repository URL:
http://dc.engconfintl.org/vaccine_vi/49
Author(s):
Schwartz, Richard M.; Hussain, Althaf I.; Chen, Mingzhong; Chen, Pefieng; Ghosh, Mridul; Cooper, Jonathan W.; O’Connell, Sarah E.; Kueltzo, Lisa A.
Tags:
RSV; trimer; pre-fusion; Engineering
abstract description
It has been known that the RSV fusion protein F is a target vaccine protein to produce a protective immune response. The VRC has shown (Ngwuta, et.al.) through binding competition assays that the amount of pre-fusion site Ø–specific antibodies correlates with neutralizing (NT) activity, whereas the pre/post-fusion site II mAbs does not correlate with neutralization. Our results indicate that RSV NT activity in human sera is primarily derived from pre-F–specific antibodies, and therefore, inducing or boosting NT activity by vaccination will be facilitated by using pre-F antigens that preserve site Ø. Therefore, the instability of the RSV pre-fusion conformation has limited the potential of this as a vaccine antigen. Therefore, the VRC has designed a structurally stabilized glycoprotein pre-fusion RSV F trimer vaccine antigen and has shown it to be highly immunogenic in preclinical studies. A description of challenges in the development of a high productivity CHO cell line, production process and product quality and antigenic characterization assays for Phase I clinical material will be presented along with comparison of pre-clinical results of research to development material.Please click Additional Files below to see the full abstract.