Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2020 Apr 25

PMID 32330425

Citations 94

Authors

Ming Te Yeh

Erika Bujaki

Patrick T Dolan

Matthew Smith

Rahnuma Wahid

John Konz

Amy J Weiner

Ananda S Bandyopadhyay

Pierre Van Damme

Ilse De Coster

Hilde Revets

Andrew Macadam

Raul Andino

Affiliations

Soon will be listed here.

Abstract

The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 5' untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.

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