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Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J - PLoS Pathog. (2015)

Bottom Line: With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance.These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients.Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.

ABSTRACT
There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

No MeSH data available.


Related in: MedlinePlus

Sequence analysis of iVDPV strains.Neighbour-joining tree representing phylogenetic relationships through the entire capsid coding sequence (2637 nt) between iVDPV isolates from the case study (shown as a number that corresponds to the date of isolation in the format ddmmyy), Sabin 2 vaccine strain and other type 2 VDPV and wild polioviruses. EMBL Data Library accession numbers for published capsid sequences are shown in the tree. Numbers at nodes indicate the percentage of 1000 bootstrap pseudoreplicates supporting the cluster. The sequence of PV1-Mahoney reference strain was introduced as an outgroup for the correct rooting of the tree. Isolates from the patient are labelled with blue circles on the tree, other iVDPV isolates are indicated in yellow, cVDPVs in red, VDPVs found in sewage samples in green and wild polioviruses in purple.
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ppat.1005114.g001: Sequence analysis of iVDPV strains.Neighbour-joining tree representing phylogenetic relationships through the entire capsid coding sequence (2637 nt) between iVDPV isolates from the case study (shown as a number that corresponds to the date of isolation in the format ddmmyy), Sabin 2 vaccine strain and other type 2 VDPV and wild polioviruses. EMBL Data Library accession numbers for published capsid sequences are shown in the tree. Numbers at nodes indicate the percentage of 1000 bootstrap pseudoreplicates supporting the cluster. The sequence of PV1-Mahoney reference strain was introduced as an outgroup for the correct rooting of the tree. Isolates from the patient are labelled with blue circles on the tree, other iVDPV isolates are indicated in yellow, cVDPVs in red, VDPVs found in sewage samples in green and wild polioviruses in purple.

Mentions: The first stool samples from this individual were tested between March and November 1995. At that time, type 2 VDPV isolates differing from the parental Sabin 2 OPV strain at between 9.9% and 11.3% of VP1 nucleotides were identified. A total of 185 subsequent samples have been obtained so far in the following years, all positive for iVDPV2 strains with virus titres shed in the stools typically around or above 4 log10 infectious particles per gram, comparable to virus titres shed by healthy vaccinees and paralytic cases infected with vaccine or wild poliovirus [16]. The latest isolate available was from 4th March 2015 showing a 17.7% VP1 sequence drift from Sabin 2 poliovirus. Phylogenetic analyses in the capsid region confirmed that the iVDPV strains were genetically related, sequentially evolved from Sabin 2 and distinct from other type 2 VDPVs and wild polioviruses (Fig 1).


Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J - PLoS Pathog. (2015)

Sequence analysis of iVDPV strains.Neighbour-joining tree representing phylogenetic relationships through the entire capsid coding sequence (2637 nt) between iVDPV isolates from the case study (shown as a number that corresponds to the date of isolation in the format ddmmyy), Sabin 2 vaccine strain and other type 2 VDPV and wild polioviruses. EMBL Data Library accession numbers for published capsid sequences are shown in the tree. Numbers at nodes indicate the percentage of 1000 bootstrap pseudoreplicates supporting the cluster. The sequence of PV1-Mahoney reference strain was introduced as an outgroup for the correct rooting of the tree. Isolates from the patient are labelled with blue circles on the tree, other iVDPV isolates are indicated in yellow, cVDPVs in red, VDPVs found in sewage samples in green and wild polioviruses in purple.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552295&req=5

ppat.1005114.g001: Sequence analysis of iVDPV strains.Neighbour-joining tree representing phylogenetic relationships through the entire capsid coding sequence (2637 nt) between iVDPV isolates from the case study (shown as a number that corresponds to the date of isolation in the format ddmmyy), Sabin 2 vaccine strain and other type 2 VDPV and wild polioviruses. EMBL Data Library accession numbers for published capsid sequences are shown in the tree. Numbers at nodes indicate the percentage of 1000 bootstrap pseudoreplicates supporting the cluster. The sequence of PV1-Mahoney reference strain was introduced as an outgroup for the correct rooting of the tree. Isolates from the patient are labelled with blue circles on the tree, other iVDPV isolates are indicated in yellow, cVDPVs in red, VDPVs found in sewage samples in green and wild polioviruses in purple.
Mentions: The first stool samples from this individual were tested between March and November 1995. At that time, type 2 VDPV isolates differing from the parental Sabin 2 OPV strain at between 9.9% and 11.3% of VP1 nucleotides were identified. A total of 185 subsequent samples have been obtained so far in the following years, all positive for iVDPV2 strains with virus titres shed in the stools typically around or above 4 log10 infectious particles per gram, comparable to virus titres shed by healthy vaccinees and paralytic cases infected with vaccine or wild poliovirus [16]. The latest isolate available was from 4th March 2015 showing a 17.7% VP1 sequence drift from Sabin 2 poliovirus. Phylogenetic analyses in the capsid region confirmed that the iVDPV strains were genetically related, sequentially evolved from Sabin 2 and distinct from other type 2 VDPVs and wild polioviruses (Fig 1).

Bottom Line: With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance.These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients.Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission.

View Article: PubMed Central - PubMed

Affiliation: Division of Virology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.

ABSTRACT
There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

No MeSH data available.


Related in: MedlinePlus