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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

Neurovirulence of iVDPV strains.The graphic represents 50% Paralytic Doses (PD50) values (with 95% Confidence Intervals) for selected poliovirus strains determined in Tg21-bx mice using the Probit method. Isolates from the patient are shown underlined.
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ppat.1005114.g002: Neurovirulence of iVDPV strains.The graphic represents 50% Paralytic Doses (PD50) values (with 95% Confidence Intervals) for selected poliovirus strains determined in Tg21-bx mice using the Probit method. Isolates from the patient are shown underlined.

Mentions: All iVDPV isolates showed reversion at the two known attenuation mutations of Sabin 2 vaccine strain: nucleotide 481 (from A to G) in the 5’ non-coding region (5’NCR) and capsid amino acid VP1-143 (from Isoleucine to Threonine) and were highly neurovirulent in transgenic mice expressing the human poliovirus receptor. The 50% paralytic dose (PD50) values were comparable to those determined for cVDPV and wild polioviruses while the Sabin 2 vaccine strain did not paralyse any animals at the highest dose that could be given (Fig 2).


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)

Neurovirulence of iVDPV strains.The graphic represents 50% Paralytic Doses (PD50) values (with 95% Confidence Intervals) for selected poliovirus strains determined in Tg21-bx mice using the Probit method. Isolates from the patient are shown underlined.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005114.g002: Neurovirulence of iVDPV strains.The graphic represents 50% Paralytic Doses (PD50) values (with 95% Confidence Intervals) for selected poliovirus strains determined in Tg21-bx mice using the Probit method. Isolates from the patient are shown underlined.
Mentions: All iVDPV isolates showed reversion at the two known attenuation mutations of Sabin 2 vaccine strain: nucleotide 481 (from A to G) in the 5’ non-coding region (5’NCR) and capsid amino acid VP1-143 (from Isoleucine to Threonine) and were highly neurovirulent in transgenic mice expressing the human poliovirus receptor. The 50% paralytic dose (PD50) values were comparable to those determined for cVDPV and wild polioviruses while the Sabin 2 vaccine strain did not paralyse any animals at the highest dose that could be given (Fig 2).

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