Limited and Localized Outbreak of Newly Emergent Type 2 Vaccine-Derived Poliovirus in Sichuan, China

Abstract

an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (>0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A 481 in the 5= untranslated region and Ile 143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead.

Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

“…In this study, none of the viruses of genomic patterns A and B (which have an unmodified Sabin 2 5′UTR sequence) was neurovirulent, whereas almost all the viruses of genomic patterns C and D caused disease in mice, confirming the crucial importance of the 5′UTR in the loss of attenuation of Sabin 2-derived recombinants. These results are consistent with observations that the 5′UTR of pathogenic type 2 cVDPVs is modified by mutations affecting the adenine nucleotide in position 481, which is known to be a major determinant of attenuation of Sabin 2, or by recombination with other EV-Cs15171819213747484950. The key role of the 5′UTR in the pathogenicity of PVs has also been demonstrated for serotypes 1 and 338515253.…”

“…Such mutations are probably necessary for the increase in fitness required for field cVDPVs to emerge as pathogenic strains. In particular, residue 143 of VP1, which is known to be a determinant of attenuation37, is generally found to be mutated in cVDPVs isolated from patients15171819214950. This result is consistent with the finding that most pathogenic cVDPVs circulate for months before causing poliomyelitis cases810.…”

Circulation of multiple serotypes of highly divergent enterovirus C in the Xinjiang Uighur Autonomous Region of China

“…Poliomyelitis associated with mutated and pathogenic poliovirus strains derived from the oral polio vaccine has been a serious public health issue in the post-eradication era especially in polio free countries such as China 15 16 . Such pathogenic circulating vaccine-derived polioviruses (cVDPVs) have been reported in many poliomyelitis outbreaks in various countries, including China 17 18 19 20 . Most cVDPVs are recombinants containing unidentified EV-C donor sequences in their non-structural region 21 22 23 24 .…”

An Insight into Recombination with Enterovirus Species C and Nucleotide G-480 Reversion from the Viewpoint of Neurovirulence of Vaccine-Derived Polioviruses

“…To date, there have been several outbreaks of cVDPVs worldwide, for example, in Egypt 10 , Hispaniola (Haiti and the Dominican Republic) 8 , The Philippines 9 , Madagascar 11 12 13 , China 14 15 16 , Indonesia 17 , Cambodia 18 , Nigeria 19 20 , and Afghanistan 21 . Some phenotypic properties of cVDPVs resemble those of wild polioviruses rather than those of vaccine-related polioviruses; these include properties such as the capacity for sustained person-to-person transmission, higher neurovirulence, critical attenuating sites either have reverted or have been exchanged out by recombination, “non-vaccine-like” antigenic properties, the ability to replicate at a higher temperature, and the ability to undergo recombination with non-polio enteroviruses (NPEVs) during circulation.…”