Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2

Equestre, Michele; Genovese, D.; Cavalieri, F.; Fiore, Lucia; Santoro, R; Bercoff, R. Perez

doi:10.1128/jvi.65.5.2707-2710.1991

Cited by 25 publications

(16 citation statements)

References 30 publications

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“…Given the lower virulence of P712, researchers and laboratories often use other WPV2 strains (e.g., MEF-1) or strains isolated from type 2 VAPP cases (e.g., P2/117) (44) or cVDPV2s as neurovirulent reference strains. (45)(46)(47)(48)(49)(50)(51) Studies suggest that susceptible vaccine recipients normally excrete OPV viruses for several weeks after immunization. (9)(10)(11)31) During this period, OPV viruses acquire greater neurovirulence and transmissibility in the gut of the vaccine recipients by selecting against the attenuating mutations through reversion (either by direct back-mutation or by selection for second-site suppressor mutations).…”

Section: Evidence Base For Modeling Opv Virus Evolutionmentioning

confidence: 99%

“…Numerous studies show potential attenuating mutations for each serotype of OPV virus based on: (1) sequence comparisons between OPV virus strains and parental WPVs, (75,76) (2) sequence comparisons and/or neurovirulence testing in monkeys or mice of recombinant virus strains (i.e., swapping genetic segments between attenuated and neurovirulent strains) and/or site-directed mutants, (47,50,(77)(78)(79)(80)(81)(82)(83)(84) (3) OPV-related virus mutant strains after exposure to high temperature, (85) (4) OPV-related virus strains excreted by immunocompetent vaccine recipients without VAPP, (48,(86)(87)(88)(89) (5) OPV-related virus strains isolated from VAPP cases, (44)(45)(46)48,(90)(91)(92)(93)(94)(95)(96)(97)(98)(99) (6) strains isolated during cVDPV outbreaks, (15,57,100,101) (7) strains excreted by immunodeficient VDPV excretors, (102-106) (8) strains obtained during sequential passages after OPV administration in humans, (107) (9) strains obtained during sequential passages of OPV-related viruses in monkey tissues, (108) and (10) strains obtained from passages in cell culture. …”

Section: Attenuation and Reversionmentioning

confidence: 99%

“…(50) Testing in monkeys of OPV2 viruses with reversion of mutations at both nt position 481 and 2909 showed an increase in the mean lesion score from about 0.27 to 1.53, compared to a mean lesion score of 1.84 for type 2 strain P2/117 isolated from a VAPP patient. (50) Analyses of viruses excreted by both asymptomatic vaccine recipients (86,88,112,115) and type 2 VAPP cases (46,48) reveal reversions of attenuating mutations at nt position 481 in the 5 UTR. Viruses isolated during type 2 cVDPV outbreaks in Egypt from 1988 to 1993 also showed reversion, recombination, and selection against the attenuating mutations at nt positions 481 and 2909, in addition to vaccine/nonvaccine recombination.…”

Section: Opv2mentioning

confidence: 99%

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Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Tebbens¹,

Pallansch

Kim³

et al. 2013

Risk Analysis

100

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The live, attenuated oral poliovirus vaccine (OPV) provides a powerful tool for controlling and stopping the transmission of wild polioviruses (WPVs), although the risks of vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived poliovirus (cVDPV) outbreaks exist as long as OPV remains in use. Understanding the dynamics of cVDPV emergence and outbreaks as a function of population immunity and other risk factors may help to improve risk management and the development of strategies to respond to possible outbreaks. We performed a comprehensive review of the literature related to the process of OPV evolution and information available from actual experiences with cVDPV outbreaks. Only a relatively small fraction of poliovirus infections cause symptoms, which makes direct observation of the trajectory of OPV evolution within a population impractical and leads to significant uncertainty. Despite a large global surveillance system, the existing genetic sequence data largely provide information about transmitted virulent polioviruses that caused acute flaccid paralysis, and essentially no data track the changes that occur in OPV sequences as the viruses transmit largely asymptomatically through real populations with suboptimal immunity. We updated estimates of cVDPV risks based on actual experiences and identified the many limitations in the existing data on poliovirus transmission and immunity and OPV virus evolution that complicate modeling. Modelers should explore the space of potential model formulations and inputs consistent with the available evidence and future studies should seek to improve our understanding of the OPV virus evolution process to provide better information for policymakers working to manage cVDPV risks.

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Section: Evidence Base For Modeling Opv Virus Evolutionmentioning

confidence: 99%

Section: Attenuation and Reversionmentioning

confidence: 99%

Section: Opv2mentioning

confidence: 99%

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Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Tebbens¹,

Pallansch

Kim³

et al. 2013

Risk Analysis

100

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“…Group 2 consisted of PV type 2 isolates and two reference strains: the attenuated Sabin PV type 2 (AY184220) and a Sabin-like type 2 PV (AY177685), which was isolated by Buttinelli et al (2003) from an immunodeficient patient soon after the onset of paralysis. Comparing the genome of AY177685 with its parental Sabin vaccine strain, it was determined that two mutations were present in positions 481 of the 5¢UTR and 2908 of VP1 (amino acid 143), known to be correlated with the neurovirulent phenotype (Minor and Dunn 1988;Equestre et al 1991;Minor 1999;Buttinelli et al 2003). Since, the PV type 2 isolates in this study were to a certain extent genetically related to this PV, therefore, AY177685 was used as a reference PV type 2 strain.…”

Section: Phylogenetic Analysis Of the 5¢utr Of The Poliovirus Genomementioning

confidence: 99%

Prevalence of vaccine-derived polioviruses in stools of immunodeficient children in South Africa

et al. 2006

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Aims: The aim of the study was to determine the prevalence of vaccine-derived polioviruses (VDPVs) in stool specimens of immunodeficient patients such as HIV-positive children (including those with an AIDS indicator condition, according to the Centres for Disease Control and Prevention classification) by applying various molecular techniques. Methods and Results: A total of 164 stool samples from HIV-positive children and 23 stool samples from healthy immunocompetent children (the control group) were analysed during 2003 and 2004. By applying a reverse transcription polymerase chain reaction (RT-PCR) in combination with a nested PCR, a total of 54 enteroviruses were detected in the stool specimens of the immunodeficient children. The use of restriction enzymes and a Sabin specific RT-triplex PCR confirmed the presence of 13 polioviruses (PVs), such as seven Sabin PV type 1, four Sabin PV type 3 and two Sabin PV type 2 isolates. The 5¢untranslated region and the VP1 capsid-encoding protein of the 13 PVs and the three PVs from the stools of the immunocompetent children were partially sequenced and their genetic relatedness was deduced from the constructed phylogenetic trees. The majority of the PVs isolated from the stools of the immunodeficient children (10 of 13 isolates) were classified as 'oral poliovirus vaccine (OPV)-like viruses', as these isolates had close sequence relationships (>99% in VP1 nucleotide sequences) to the original Sabin PV vaccine strains. Three PVs showed £99% VP1 sequence identity to the Sabin PV vaccine strains and were classified as 'suspected' immunodeficient VDPVs (iVDPVs). All of the OPV-like isolates and the 'suspected' iVDPVs carried mutations at specific positions in their partially sequenced regions, which have been associated with reversion of the attenuated Sabin PV vaccine strains to increased neurovirulence. Conclusions: Thus, this study adds further evidence to the observation that immunodeficient individuals may excrete OPV strains with potential neurovirulent phenotypes. Significance and Impact of the Study: Prolonged excretion of PVs by immunodeficient individuals is of major concern, because continued replication of PVs in the human gut could result in the reversion of these viruses to greater neurovirulence. When exposed to OPV, immunodeficient patients may become chronically infected, spreading potentially neurovirulent VDPVs for many months or years to close contacts and children who are no longer being vaccinated after termination of OPV vaccination in the near future.

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“…Stability of Sabin 1-specific nucleotides in vivo. Sequence analysis of viruses isolated from patients with VAPP indicates that genetic determinants of temperature sensitivity and/or attenuation of vaccine PV strains are selected against in vivo (12,13,15,26,28,37). To determine the possible selection pressure in vivo against some of the Sabin 1 nucleotides which differentiate the 3Ј-terminal part of Sabin 1 genome from that of Mahoney, we analyzed the sequences of 22 strains isolated from patients with VAPP.…”

Section: Downloaded Frommentioning

confidence: 99%

Mapping of mutations contributing to the temperature sensitivity of the Sabin 1 vaccine strain of poliovirus

Georgescu

Tardy-Panit

Guillot

et al. 1995

J Virol

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The temperature-sensitive and attenuated phenotypes of the Sabin type 1 vaccine strain of poliovirus result from numerous point mutations which occurred in the virulent Mahoney virus parent. One of these mutations is located in a 3D polymerase (3D pol ) codon (U-62033C, Tyr-733His) and is involved in attenuation in common mice (M. Tardy-Panit, B. Blondel, A. Martin, F. Tekaia, F. Horaud, and F. Delpeyroux, J. Virol. 67: [4630][4631][4632][4633][4634][4635][4636][4637][4638] 1993). This mutation also appears to contribute to temperature sensitivity, in association with at least 1 other of the 10 mutations of the 3-terminal part of the genome including the 3D pol coding and 3 noncoding regions. To map the other mutation(s), we constructed poliovirus mutants by mutagenesis and recombination of Mahoney and Sabin 1 cDNAs. Characterization of these poliovirus mutants showed that a second mutation in a 3D pol codon (C-70713U, Thr-3623Ile) contributes to temperature sensitivity. A mutation in the 3 noncoding region of the genome (A-74413G), alone or linked to another mutation (U-74103C), also appeared to be involved in this phenotype. The temperature-sensitive effect associated with the 3-terminal part of the Sabin 1 genome results from the cumulative and/or synergistic effects of at least three genetic determinants, i.e., the His-73 and Ile-362 codons of 3D pol and nucleotide G-7441. Sequence analysis of strains isolated from patients with vaccine-associated paralytic poliomyelitis showed that these genetic determinants are selected against in vivo, although the Ile-362 codon appeared to be more stable than either the His-73 codon or G-7441. These genetic determinants may contribute to the safety of Sabin 1 in vaccinees.Poliovirus (PV), an enterovirus of the Picornaviridae family, is the causative agent of poliomyelitis and is classified into three distinct serotypes. It replicates in the human digestive tract and may induce paralysis by infecting and destroying motor neurons (5, 10). Poliomyelitis has been effectively controlled by the use of inactivated or live attenuated vaccines. Attenuated strains of all three serotypes have been selected by numerous passages of wild-type strains in monkey tissues in vivo and in vitro (43). These strains (Sabin 1, 2, and 3), which replicate in the human gut and induce a strong immunity, have a good safety record. However, in a small number of cases, vaccination is associated with paralytic poliomyelitis (34). Vaccine-associated paralytic poliomyelitis (VAPP) may result from the genetic variability (point mutations and recombination) of the Sabin strains. Indeed, neurovirulent vaccine-derived strains are found in the gut of healthy vaccinees and in the central nervous system of patients with VAPP (16, 31). VAPP is most frequently associated with Sabin 2 and Sabin 3 and rarely with Sabin 1 (3, 37). Analysis of the attenuation determinants of Sabin 1 could lead to a better understanding of the safety of this strain in vaccinees.PV is composed of an icosahedral protein shell which cont...

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Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2

Cited by 25 publications

References 30 publications

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

Prevalence of vaccine-derived polioviruses in stools of immunodeficient children in South Africa

Mapping of mutations contributing to the temperature sensitivity of the Sabin 1 vaccine strain of poliovirus

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