Limits...
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

Antigenic structure of iVDPV strains.Radial diagrams representing the reactivity of poliovirus strains with Sabin 2-specific monoclonal antibodies. The results are shown as OD values at 492nm obtained in ELISA assays and expressed as normalised values relative to those obtained with antibody 1102 which reacted with all poliovirus strains. These values denote the average of two duplicate assays. Monoclonal antibodies used in the assay in the order 1 to 14 shown in the graph (from the top and clockwise), with antigenic site specificity shown in brackets, were: 969 (site 1), 435 (1), 433 (1), 434 (1), 436 (1), 1231 (2a), 1247 (2a), 1269 (2a), 1037 (2b), 1050 (3a), 1102 (3b), 1103 (3b), 1121 (3b) and 1051 (3b). Sabin 2 vaccine virus, iVDPV isolates from the patient (160198, 190100, 080503, 071108 and 171012), cVDPV strain MAD029 and wild strains (EGY42, EGY52, VEN59, MOR78 and KUW80) were used in the assays.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4552295&req=5

ppat.1005114.g003: Antigenic structure of iVDPV strains.Radial diagrams representing the reactivity of poliovirus strains with Sabin 2-specific monoclonal antibodies. The results are shown as OD values at 492nm obtained in ELISA assays and expressed as normalised values relative to those obtained with antibody 1102 which reacted with all poliovirus strains. These values denote the average of two duplicate assays. Monoclonal antibodies used in the assay in the order 1 to 14 shown in the graph (from the top and clockwise), with antigenic site specificity shown in brackets, were: 969 (site 1), 435 (1), 433 (1), 434 (1), 436 (1), 1231 (2a), 1247 (2a), 1269 (2a), 1037 (2b), 1050 (3a), 1102 (3b), 1103 (3b), 1121 (3b) and 1051 (3b). Sabin 2 vaccine virus, iVDPV isolates from the patient (160198, 190100, 080503, 071108 and 171012), cVDPV strain MAD029 and wild strains (EGY42, EGY52, VEN59, MOR78 and KUW80) were used in the assays.

Mentions: As a consequence, the iVDPV strains did not react at all with monoclonal antibodies against most of the known neutralising antibody sites (Fig 3). It was of interest that all isolates tested did react with antibodies specific for antigenic site 3b (1102 and 1103). In contrast, the wild polioviruses strains analysed, which span almost four decades in time and which were isolated in geographically distant locations, exhibited an antigenic structure much closer to that of Sabin 2 virus, reacting with at least one monoclonal antibody specific for each antigenic site (Fig 3). A cVDPV strain from Madagascar [21] also reacted with most monoclonal antibodies.


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)

Antigenic structure of iVDPV strains.Radial diagrams representing the reactivity of poliovirus strains with Sabin 2-specific monoclonal antibodies. The results are shown as OD values at 492nm obtained in ELISA assays and expressed as normalised values relative to those obtained with antibody 1102 which reacted with all poliovirus strains. These values denote the average of two duplicate assays. Monoclonal antibodies used in the assay in the order 1 to 14 shown in the graph (from the top and clockwise), with antigenic site specificity shown in brackets, were: 969 (site 1), 435 (1), 433 (1), 434 (1), 436 (1), 1231 (2a), 1247 (2a), 1269 (2a), 1037 (2b), 1050 (3a), 1102 (3b), 1103 (3b), 1121 (3b) and 1051 (3b). Sabin 2 vaccine virus, iVDPV isolates from the patient (160198, 190100, 080503, 071108 and 171012), cVDPV strain MAD029 and wild strains (EGY42, EGY52, VEN59, MOR78 and KUW80) were used in the assays.
© Copyright Policy
Related In: Results  -  Collection

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

ppat.1005114.g003: Antigenic structure of iVDPV strains.Radial diagrams representing the reactivity of poliovirus strains with Sabin 2-specific monoclonal antibodies. The results are shown as OD values at 492nm obtained in ELISA assays and expressed as normalised values relative to those obtained with antibody 1102 which reacted with all poliovirus strains. These values denote the average of two duplicate assays. Monoclonal antibodies used in the assay in the order 1 to 14 shown in the graph (from the top and clockwise), with antigenic site specificity shown in brackets, were: 969 (site 1), 435 (1), 433 (1), 434 (1), 436 (1), 1231 (2a), 1247 (2a), 1269 (2a), 1037 (2b), 1050 (3a), 1102 (3b), 1103 (3b), 1121 (3b) and 1051 (3b). Sabin 2 vaccine virus, iVDPV isolates from the patient (160198, 190100, 080503, 071108 and 171012), cVDPV strain MAD029 and wild strains (EGY42, EGY52, VEN59, MOR78 and KUW80) were used in the assays.
Mentions: As a consequence, the iVDPV strains did not react at all with monoclonal antibodies against most of the known neutralising antibody sites (Fig 3). It was of interest that all isolates tested did react with antibodies specific for antigenic site 3b (1102 and 1103). In contrast, the wild polioviruses strains analysed, which span almost four decades in time and which were isolated in geographically distant locations, exhibited an antigenic structure much closer to that of Sabin 2 virus, reacting with at least one monoclonal antibody specific for each antigenic site (Fig 3). A cVDPV strain from Madagascar [21] also reacted with most monoclonal antibodies.

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