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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

Location of mutations in iVDPV isolate 160198.Molecular surface diagram of the three-dimensional structure of type 2 wild poliovirus strain Lansing viewed from the outside of the virion [25]. A pentameric unit is represented. The virus particle consists of 60 protomers. Each protomer contains a single copy of VP1, VP2, VP3, and VP4 arranged in icosahedral symmetry. The location of mutations found in known antigenic sites of iVDPV isolate 160198 with respect to Sabin 2 vaccine strain are shown in red, other amino acid changes from Sabin 2 are displayed in cyan. The image was generated using PyMOL Molecular Graphics System, Version 1.7.0.3 software (Schrödinger, LLC).
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ppat.1005114.g004: Location of mutations in iVDPV isolate 160198.Molecular surface diagram of the three-dimensional structure of type 2 wild poliovirus strain Lansing viewed from the outside of the virion [25]. A pentameric unit is represented. The virus particle consists of 60 protomers. Each protomer contains a single copy of VP1, VP2, VP3, and VP4 arranged in icosahedral symmetry. The location of mutations found in known antigenic sites of iVDPV isolate 160198 with respect to Sabin 2 vaccine strain are shown in red, other amino acid changes from Sabin 2 are displayed in cyan. The image was generated using PyMOL Molecular Graphics System, Version 1.7.0.3 software (Schrödinger, LLC).

Mentions: Despite the extensive antigenic changes found in iVDPV strains (Fig 4), human sera readily neutralised iVDPV isolate 160198, the most antigenically divergent strain (Fig 5). This isolate was the only one obtained by plaque purification so it might represent a minor variant with slightly different antigenic makeup.


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)

Location of mutations in iVDPV isolate 160198.Molecular surface diagram of the three-dimensional structure of type 2 wild poliovirus strain Lansing viewed from the outside of the virion [25]. A pentameric unit is represented. The virus particle consists of 60 protomers. Each protomer contains a single copy of VP1, VP2, VP3, and VP4 arranged in icosahedral symmetry. The location of mutations found in known antigenic sites of iVDPV isolate 160198 with respect to Sabin 2 vaccine strain are shown in red, other amino acid changes from Sabin 2 are displayed in cyan. The image was generated using PyMOL Molecular Graphics System, Version 1.7.0.3 software (Schrödinger, LLC).
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005114.g004: Location of mutations in iVDPV isolate 160198.Molecular surface diagram of the three-dimensional structure of type 2 wild poliovirus strain Lansing viewed from the outside of the virion [25]. A pentameric unit is represented. The virus particle consists of 60 protomers. Each protomer contains a single copy of VP1, VP2, VP3, and VP4 arranged in icosahedral symmetry. The location of mutations found in known antigenic sites of iVDPV isolate 160198 with respect to Sabin 2 vaccine strain are shown in red, other amino acid changes from Sabin 2 are displayed in cyan. The image was generated using PyMOL Molecular Graphics System, Version 1.7.0.3 software (Schrödinger, LLC).
Mentions: Despite the extensive antigenic changes found in iVDPV strains (Fig 4), human sera readily neutralised iVDPV isolate 160198, the most antigenically divergent strain (Fig 5). This isolate was the only one obtained by plaque purification so it might represent a minor variant with slightly different antigenic makeup.

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