Isolation and characterization of a Sabin 3/Sabin 1 recombinant vaccine-derived poliovirus from a child with severe combined immunodeficiency

Virus Res. 2022 Jan 15:308:198633. doi: 10.1016/j.virusres.2021.198633. Epub 2021 Nov 15.

Abstract

An 8-month-old child diagnosed with severe combined immunodeficiency (SCID) was found to be excreting vaccine-derived poliovirus (VDPVs). Five stool samples from the child and stool samples from 24 contacts were collected during the following 7 months. Complete genome sequence by next generation sequencing (NGS) identified 0.7 to 1.4% nucleotide substitutions in the capsid P1 region of the first and the last isolates compared with Sabin 3 strain. Simplot analysis revealed that all isolates were Sabin 3/Sabin 1 recombinants, sharing a single recombination breakpoint in the 2C region. Multiple nucleotide variants were identified in the 5'UTR (T472→C and G395→A); amino acid mutations were identified in residues at VP1-6 (Thr to Ile), VP1-105 (Met to Thr), VP1-286 (Arg to Lys), VP2-155 (Lys to Glu), VP3-59 (Ser to Asn) and VP3-91 (Phe to Ser). These variants were commonly observed in other PV strains, which may contribute to attenuation and temperature sensitivity. None of the 24 tested contacts of the patient and related transmits was found to be infected with poliovirus. Our study provides a rapid and reliable method for the characterization of VDPV research in Poliovirus infection. In post-OPV era, immunodeficient people with persistent and chronic infection remain a major challenge for polio eradication in China.

Keywords: Complete genome sequence; OPV; Poliovirus; Recombinant vaccine-derived poliovirus; Sabin strains; VDPV; iVDPV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Infant
  • Nucleotides
  • Poliomyelitis*
  • Poliovirus Vaccine, Oral / adverse effects
  • Poliovirus* / genetics
  • Severe Combined Immunodeficiency* / complications
  • Vaccines, Synthetic

Substances

  • Nucleotides
  • Poliovirus Vaccine, Oral
  • Vaccines, Synthetic