Development of a stabilized trimer pre-fusion RSV F recombinant viral glycoprotein vaccine
June 12-17, 2016
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.
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Richard M. Schwartz, Althaf I. Hussain, Mingzhong Chen, Pefieng Chen, Mridul Ghosh, Jonathan W. Cooper, Sarah E. O’Connell, and Lisa A. Kueltzo, "Development of a stabilized trimer pre-fusion RSV F recombinant viral glycoprotein vaccine" in "Vaccine Technology VI", Laura Palomares, UNAM, Mexico Manon Cox, Protein Sciences Corporation, USA Tarit Mukhopadhyay, University College London, UK Nathalie Garçon, BIOASTER Technology Research Institute, FR Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/vaccine_vi/49