Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses

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.

Evaluating stability of attenuated Sabin and two novel type 2 oral poliovirus vaccines in children

“…3 and Supplementary Table 3 for nOPV2-c1. Evolution of the shed virus was consistent with observations from prior studies in adult recipients of nOPV2-c1 9 . SNPs in the relocated cre at nucleotide 123 and/or 179, which strengthens U-G base pair to C-G or U-A were observed in all EES day 4 to 28 at variable levels up to 100% frequency.…”

“…In addition, to assess the genetic stability of the genome in shed virus, next-generation sequencing (NGS) was conducted. NGS and mTgmNVT were used to evaluate virus shed in a subset of stool samples (the exploratory endpoint specimen, EES) from clinical trial participants, as described in METHODS 9 .…”

“…Two novel OPV2 candidates have recently been developed and advanced through Phase 1 and 2 clinical studies with the goal of providing similar protection as mOPV2 but with reduced risk of loss of attenuation 9 – 11 . Both candidates include a genetically stabilized domain V termed S15, which was designed to attenuate the strain to a similar degree as the Sabin strains, while avoiding the possibility of loss of attenuation via single nucleotide changes.…”

“…In addition to having an acceptable clinical safety profile and non-inferior immunogenicity, the novel vaccines are intended to retain their attenuated phenotype in a manner superior to Sabin OPV2. Details of a workflow to examine the genetic heterogeneity and neurovirulence of fecally-shed virus using next-generation sequencing and mouse neurovirulence assay have recently been described 9 . Here, this paper reports the first use of this workflow to provide a head-to-head comparison of shed nOPV2 candidates with shed Sabin-2 from two clinical trials in Panamanian children.…”

Editorial: Codon Usage and Dinucleotide Composition of Virus Genomes: From the Virus-Host Interaction to the Development of Vaccines

“…Noteworthy, based on some of the above principles, candidate poliovirus vaccines have been developed and employed in the final phases of the poliovirus eradication (Burns et al, 2009 ; Van Damme et al, 2019 ; Konopka-Anstadt et al, 2020 ; De Coster et al, 2021 ; Saez-Llorens et al, 2021 ; Wahid et al, 2021 ).…”