Effect of different immunisation schedules on the excretion and reversion of oral poliovaccine strains

Minor, Philip D.; Dunn, Glynis; Ramsay, Mary; Brown, David J.

doi:10.1002/jmv.20250

Cited by 27 publications

(42 citation statements)

References 9 publications

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“…The current study demonstrated that 100% of infants shed OPV3 as estimated by both methods, likely reflecting a higher sensitivity of PCR methods than tissue culture for the detection of OPV3. Data from banked stool samples obtained from first-dose OPV vaccinees in Western countries demonstrated shedding in 95% of vaccinees for all three serotypes (17) and in 65% of vaccinees for OPV3 (22). This study confirms high shedding rates in a country where OPV continues to be used.…”

Section: Discussionsupporting

confidence: 64%

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

et al. 2007

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A uracil-to-cytosine mutation at nucleotide position 472 of oral poliovirus vaccine type 3 (OPV3) contributes to the development of vaccine-associated paralytic poliomyelitis (VAPP). To analyze OPV3 shedding patterns, we previously used the multistep method of mutant analysis by PCR and enzyme cleavage (MAPREC). This involves conventional reverse transcription-PCR to detect OPV3, followed by a restriction digest to quantify position 472 reversion. Real-time PCR detects and quantifies nucleic acid as PCR occurs and avoids postreaction processing. The goal of this study was to compare a real-time PCR method to MAPREC. Seventy-three stool samples from Mexican OPV recipients underwent the reverse transcription-PCR step of MAPREC and real-time PCR. Real-time PCR identified 23% more OPV3-positive samples than conventional reverse transcription-PCR. When reversion was compared, the revertant proportion (RP), defined as the percentage of revertants in a sample, differed by <10% in 21/25 (84%) samples. The four samples differing by >10% were obtained within 5 days of OPV administration. The real-time PCR assay identified samples with an RP of >85% with 94% sensitivity and 86% specificity compared to MAPREC. The mean difference in RP between the two methods was 3.6% (95% confidence interval, ؊0.3 to 7.5%). Real-time PCR methods reliably detect OPV3, and reversion estimates correlate more consistently with MAPREC when OPV3 reversion rates are high. Detecting VAPP-related mutations by real-time PCR is rapid and efficient and can be useful in monitoring ongoing global polio eradication efforts.Vaccination using the trivalent, live attenuated oral poliomyelitis vaccine (OPV) led to the elimination of poliomyelitis in the United States and several regions of the world (15, 26). Specifically, OPV is transmitted by the fecal-oral route and by contact with pharyngeal secretions and thereby confers immunity to unvaccinated individuals (10). However, OPV strains also undergo mutations and recombination during replication in humans (13), with the attenuating OPV sequences often being selected against in the human intestinal tract (21). The transmission of these revertant strains leads to vaccine-associated paralytic poliomyelitis (VAPP) (2).Although many industrialized countries have adopted inactivated polio vaccine (IPV) into their immunization programs due to the risk of VAPP (7), several resource-poor nations cannot afford this policy change. Currently, the global VAPP burden is estimated to be 250 to 500 cases annually (14), with most cases occurring in resource-poor settings, and the risk of paralytic polio due to OPV will continue until as long as the oral vaccine is in use.Most cases of VAPP in the United States and in Latin America were due to serotype 3 (1, 7). A point mutation at position 472 of Sabin OPV3 within the 5Ј noncoding region and its internal ribosomal entry site is known to be an attenuating sequence for this serotype, and reversion of this nucleotide has been associated with VAPP (9). These back-mutations of ...

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Section: Discussionsupporting

confidence: 64%

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

et al. 2007

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“…Viruses that followed the second pathway first incorporated, by day 21, a mutation at nucleotide 476 that converted a UU mismatch to an AU base pair, increasing the stability of domain V (62). This mutation had also been seen before in type 1 isolates from vaccinees (12,51). Domain V was further stabilized by the introduction between days 21 and 49 of the reversion at nucleotide 480 mentioned above.…”

Section: Phylogenetic Analysis Of Poliovirus Isolatessupporting

confidence: 73%

“…5). Isolates found on days 49, 63, 88, and 102 had acquired a mutation at nucleotide 480 with respect to Sabin 1, which is a straight reversion to the sequence present in Mahoney virus and is commonly found in isolates from VAPP patients and healthy vaccinees (19,34,51). This mutation restores an AU base pair, strengthening the stem structure in domain V (62).…”

Section: Phylogenetic Analysis Of Poliovirus Isolatesmentioning

confidence: 99%

Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient

Odoom

Yunus

Dunn

et al. 2008

J Virol

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The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperaturesensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5 noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative.

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“…Three different mutations in domain V of Sabin 1 are selected during replication in the gut (5,30), all of which strengthen base pairing: G3A at position 480, U3C at position 525, and U3A at position 476. Nucleotides 480 and 525 form a base pair (positions 483/528 in Fig.…”

Section: Genetic Stability (I) Type 3 Virusesmentioning

confidence: 99%

“…For the type 1 strain, the G-U base pair involving bases 480 and 525 can mutate to the wild-type A-U base pair by a mutation of base 480 or to a G-C pair by a mutation at base 525. In about 10% of isolates, a U-U mismatch in the type 1 stem changes to a U-A base pair without other changes but with the same effect on thermodynamic stability (5,30).…”

mentioning

confidence: 99%

Rational Design of Genetically Stable, Live-Attenuated Poliovirus Vaccines of All Three Serotypes: Relevance to Poliomyelitis Eradication

Macadam

Ferguson

Stone

et al. 2006

J Virol

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The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains. The appearance of such strains depends on the prevailing circumstances but poses a severe obstacle to strategies for stopping vaccination. Vaccine strains that are incapable of reversion at a measurable rate would provide a possible solution. Here, we describe the constructions of strains of type 3 poliovirus that are stabilized by the introduction of four mutations in the 5 noncoding region compared to the present vaccine. The strains are genetically and phenotypically stable under conditions where the present vaccine loses the attenuating mutation in the 5 noncoding region completely. Type 1 and type 2 strains in which the entire 5 noncoding regions of Sabin 1 and Sabin 2 were replaced exactly with that of one of the type 3 strains were also constructed. The genetic stability of 5 noncoding regions of these viruses matched that of the type 3 strains, but significant phenotypic reversion occurred, illustrating the potential limitations of a rational approach to the genetic stabilization of live RNA virus vaccines.Poliomyelitis is caused by poliovirus, a member of the picornavirus family that occurs in three serotypes such that immunity to one serotype does not protect against the other two.

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Effect of different immunisation schedules on the excretion and reversion of oral poliovaccine strains

Cited by 27 publications

References 9 publications

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

Shedding and Reversion of Oral Polio Vaccine Type 3 in Mexican Vaccinees: Comparison of Mutant Analysis by PCR and Enzyme Cleavage to a Real-Time PCR Assay

Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient

Rational Design of Genetically Stable, Live-Attenuated Poliovirus Vaccines of All Three Serotypes: Relevance to Poliomyelitis Eradication

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