학술논문
Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses
Document Type
article
Author
Rahnuma Wahid; Laina Mercer; Andrew Macadam; Sarah Carlyle; Laura Stephens; Javier Martin; Konstantin Chumakov; Majid Laassri; Svetlana Petrovskaya; Saskia L. Smits; Koert J. Stittelaar; Chris Gast; William C. Weldon; Jennifer L. Konopka-Anstadt; M. Steven Oberste; Pierre Van Damme; Ilse De Coster; Ricardo Rüttimann; Ananda Bandyopadhyay; John Konz
Source
npj Vaccines, Vol 6, Iss 1, Pp 1-11 (2021)
Subject
Language
English
ISSN
2059-0105
Abstract
Abstract Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.