Engineering enhanced vaccine cell lines to eradicate vaccine-preventable diseases: The polio end game

Sabine M.G. Van Der Sanden, Weilin Wu, Naomi Dybdahl-Sissoko, William C. Weldon, Paula Brooks, Jason O'Donnell, Les P. Jones, Cedric Brown, S. Mark Tompkins, M. Steven Oberste, Jon Karpilow, Ralph A. Tripp

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccinepreventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine.

Original languageEnglish
Pages (from-to)1694-1704
Number of pages11
JournalJournal of Virology
Volume90
Issue number4
DOIs
Publication statusPublished - 2016
Externally publishedYes

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