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PubMed1987

Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States.

Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.

Drug Administration Schedule↗
PubMed1991

Cellular and humoral immune responses to poliovirus in mice: a role for helper T cells in heterotypic immunity to poliovirus.

Immunization of BALB/c mice with a single dose of the Sabin type 1, type 2 or type 3 poliovirus vaccine strains stimulated cross-reactive T helper cell responses detected by both in vitro proliferation and interleukin (IL)-2/IL-4 production. Although the polyclonal T cell responses were cross-reactive, the results also suggest that a proportion of the T cells were directed against serotype-specific determinants. In contrast, neutralizing antibodies, assayed in the serum from the same animals, were predominantly serotype-specific and only reached significant titres after secondary immunization. A comparison of the immunogenicity of poliovirus administered subcutaneously in Freund's complete adjuvant or intraperitoneally as an alum precipitate or without adjuvant, showed that optimum responses were obtained by immunization with virus in the presence of alum. An examination of the effect of heterotypic priming showed that immunization with type 2 virus primed for a secondary antibody response to each of the three serotypes, whereas priming with type 1 or type 3 viruses could only generate a secondary antibody response to the homologous virus or to type 2 virus.

Animals↗
PubMed2001

Cost-effectiveness analysis of changing from live oral poliovirus vaccine to inactivated poliovirus vaccine in Australia.

OBJECTIVE: Estimate the economic impact of introducing inactivated poliovirus vaccine (IPV) into the Australian childhood immunisation schedule to eliminate vaccine-associated paralytic poliomyelitis (VAPP). METHODS: Cost-effectiveness of two different four-dose IPV schedules (monovalent vaccine and IPV-containing combination vaccine) compared with the current four-dose oral poliovirus vaccine (OPV) schedule for Australian children through age six years. Model used estimates of VAPP incidence, costs, and vaccine utilisation and price obtained from published and unpublished sources. Main outcome measures were total costs, outcomes prevented, and incremental cost-effectiveness, expressed as net cost per case of VAPP prevented. RESULTS: Changing to an IPV-based schedule would prevent 0.395 VAPP cases annually. At $20 per dose for monovalent vaccine and $14 per dose for the IPV component in a combination vaccine, the change would incur incremental, annual costs of $19.5 million ($49.3 million per VAPP case prevented) and $6.7 million ($17.0 million per VAPP case prevented), respectively. Threshold analysis identified break-even prices per dose of $1 for monovalent and $7 for combination vaccines. CONCLUSIONS: Introducing IPV into the Australian childhood immunisation schedule is not likely to be cost-effective unless it comes in a combined vaccine with the IPV-component price below $10. IMPLICATIONS: More precise estimates of VAPP incidence in Australia and IPV price are needed. However, poor cost-effectiveness will make the decision about switching from OPV to IPV in the childhood schedule difficult.

Australia↗
PubMed2000

Assessment of poliovirus eradication in Japan: genomic analysis of polioviruses isolated from river water and sewage in toyama prefecture.

Seventy-eight poliovirus strains isolated from river water and sewage in Toyama Prefecture, Japan, during 1993 to 1995 were characterized by the PCR-restriction fragment length polymorphism (RFLP) method and by partially sequencing the VP3 and VP1 regions of the viral genome. Of these isolates, 36 were identified as Sabin vaccine strains, and 42 were identified as vaccine variant strains that had less than 1.4% nucleotide divergence from the Sabin strains, including 7 isolates with patterns different from those of Sabin strains as determined by PCR-RFLP analysis. These findings suggest that wild-type poliovirus was not circulating in Toyama Prefecture.

Fresh Water↗
PubMed2000

Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model.

We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis.

Adolescent↗
PubMed1979

Polioviruses and other enteroviruses in urban sewage from Laval (Canada): presence of non-vaccinal strains of poliovirus.

During a 13-month period (August 1, 1977-August 31, 1978) 55 samples of 2-4 L of raw sewage from an urban residential area were collected and studied for the presence of human enteroviruses. Viruses were recovered from 47 (90.5%) of the samples. Of the 201 viral isolates propagated, 180 (89.5%) were identified by the serum neutralization test as poliovirus types 1,2, or 3; 16 (8%) were identified as coxsackie B viruses; and 5 (2.5%) could not be identified by the methods used. While all polioviruses, types 2 and 3 isolates, were vaccine-like (rct-/d-) or intermediate strains, 14 poliovires, type 1 out of 55 selected isolates, were found to be non-vaccine-like (rct+/d+), 8 were rct-/d-), and 33 were intermediate strains. Out of nine samples submitted to the serodifferentiation (McBride) test, six poliovires, type 1 rct+/d+ and three rct+/d-, were related to wild strains.

Enterovirus↗
PubMed1994

Lessons from Cuba: mass campaign administration of trivalent oral poliovirus vaccine and seroprevalence of poliovirus neutralizing antibodies.

The immunogenicity of trivalent oral poliovirus vaccine (TOPV), which is less effective in tropical than in temperate areas, may potentially be improved in several ways, including increasing the number of doses. Little information is available on TOPV when more than 6 doses are given. The situation in Cuba provides a unique opportunity to relate the seroprevalence of neutralizing antibodies to the dose of TOPV because Cuba has not reported culture-confirmed poliomyelitis since 1973 and TOPV is only administered in twice yearly 1-week mass immunization campaigns. Sera from 2000 children nationwide were studied for neutralizing antibody among children who received 0, 2, 4, 6 and 8 doses of TOPV. These doses were administered in the period 1989-91, when TOPV (from the USSR) was being used with 500,000, 200,000, and 300,000 median tissue-culture-infecting doses (TCID50) for types 1, 2 and 3, respectively--the 5:2:3 formulation. Seroprevalence of neutralizing antibody after two TOPV doses was 91.5% for type 1, 90.8% for type 2, and 45.9% for type 3. Seroprevalence of type-3 neutralizing antibody after 6 doses remained low (73.4%), but increased to 83.5% after 8 doses (P < 0.05). Although 16.5% of the children remained unprotected for type-3 infection even after 8 doses, mass campaign immunization strategies were sufficient to eradicate the transmission of wild poliovirus in Cuba. Because the seroprevalence of type-1 neutralizing antibody was high (91.5%) after two campaign doses, additional studies using different formulations are needed to determine whether simultaneous improvement in the type-3 response to two campaign doses can be achieved.

Antibodies, Viral↗
PubMed1993

Poliovirus receptor on human blood cells: a possible extraneural site of poliovirus replication.

In order to determine whether any primary human blood cells have the ability to replicate poliovirus (PV), peripheral blood cell components were isolated and analyzed for their cell surface expression of the poliovirus receptor (PVR). Following two-color immunfluoresence staining with lineage-specific markers, the cells were analyzed by flow-cytometric methods. PVR cell surface expression was detected on most mononuclear cells expressing CD14, a marker for mononuclear phagocytes. There was no PVR cell surface expression on platelets and extremely low levels on polymorphonuclear leukocytes. Mononuclear leukocytes from Ficoll density centrifugation were found to support PV replication. The finding of PVR on mononuclear phagocytes and the ability of primary human blood cells to support PV replication in the absence of cultivation has implications for both the normal and pathogenic role of PVR.

Flow Cytometry↗
PubMed1995

Cell clones cured of persistent poliovirus infection display selective permissivity to the wild-type poliovirus strain Mahoney and partial resistance to the attenuated Sabin 1 strain and Mahoney mutants.

We report the isolation and characterization of HEp-2c cell clones obtained after two successive persistent poliovirus (PV) infections. Once cured, some of the cell clones displayed selective permissivity toward the wild-type Mahoney strain and partial resistance to particular mutants of this strain, including the Sabin 1 strain. Two cell clones, CI 4 and CI 10, were studied in greater detail. The cytopathic effects of Mahoney infection were comparable in the cell clones and in HEp-2c cells. The cytopathic effects of infection by Sabin 1 or Mahoney mutants were greatly delayed in CI 4 and CI 10. In the genomic region encoding the capsid proteins, determinants involved in the resistance of the cell clones to the Mahoney mutants were localized in the amino-terminal part of VP1 (amino acids 22 and 43), the B-C loop of VP1 (amino acids 94-102), and the loop of VP3 connecting its amino-terminal to beta strand B (amino acid 60). These genomic regions are thought to be involved in the early steps of viral infection. Virus adsorption was slower and less efficient on CI 10 cells than on parental HEp-2c cells. Virus adsorption was faster on CI 4 than on HEp-2c cells, and at least as efficient, but there was less receptor-induced structural modification of the capsid, a step that is required for decapsidation. Furthermore, infection of CI 4 by a Mahoney mutant in which the B-C loop of VP1 has been deleted was affected in the later steps of infection. These results indicate that, in cells cured of persistent PV infection, poliovirus multiplication was restricted at several stages and particularly at two steps of virus entry: adsorption and/or the uncoating transitions following adsorption onto the receptor.

Base Sequence↗
PubMed1989

Self-catalyzed linkage of poliovirus terminal protein VPg to poliovirus RNA.

The poliovirus terminal protein, VPg, was covalently linked to poliovirus RNA in a reaction that required synthetic VPg, Mg2+, and a replication intermediate synthesized in vitro. The VPg linkage reaction did not require the viral polymerase, host factor, or ribonucleoside triphosphates and was specific for template-linked minus-strand RNA synthesized on poliovirion RNA. The covalent nature of the bond between VPg and the RNA was demonstrated by the isolation of VPg-pUp from VPg-linked RNA. A model is proposed in which the tyrosine residue in VPg forms a phosphodiester bond with the 5'UMP in minus-strand RNA in a self-catalyzed transesterification reaction. It appears that either the RNA, VPg, or a combination of both forms the catalytic center for this reaction.

Base Sequence↗
PubMed2003

Towards an understanding of the poliovirus replication complex: the solution structure of the soluble domain of the poliovirus 3A protein.

Poliovirus is a positive-strand RNA virus and the prototypical member of the Picornaviridae family. Upon infection, the viral RNA genome is translated from a single open reading frame into a polypeptide which undergoes a series of cleavages to ultimately form four structural and seven non-structural proteins. A replication complex is then formed which replicates the viral genome into negative and positive strands for further translation, replication, and packaging into viral progeny. Poliovirus 3A protein (3A) is a critical component of the viral replication complex and is the putative target of enviroxime, an antiviral drug shown to block viral replication. 3A also inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport, a function which may play a key role in viral evasion from the host immune response. 3A, an 87-residue protein consisting of a soluble N terminus and a hydrophobic C terminus, is formed by the cleavage of the precursor protein 3AB into 3A and 3B (VPg). Although they differ by only 22 residues, the precursor protein 3AB and its cleavage product 3A have distinct functions in viral replication. We have determined the structure of the soluble, N-terminal domain of 3A (3A-N) using NMR spectroscopy. We show that 3A-N exists as a symmetric dimer, and each monomer consists of an alpha-helical hairpin with unstructured, yet functional, N- and C termini. We also show that the 3A-N structure contains a negatively charged surface patch and provides a context for interpreting the biochemical characteristics of a number of previously reported 3A and 3AB mutants.

Amino Acid Sequence↗
PubMed2002

Evaluation of poliovirus vaccines for pestivirus contamination: non-specific amplification of poliovirus sequences by pan-pestivirus primers.

Two lots of polyvalent live vaccines for human use against poliovirus were tested by reverse transcriptase (RT) and nested PCR for the presence of contaminating pestivirus RNA. By RT-PCR, samples from both lots showed a band of approximately 450 bp instead of 300 bp for the reference pestivirus strain used as positive control. After nested PCR, the template DNA (450 bp product) was not amplified, suggesting non-specificity of the previous amplification. Sequencing analysis confirmed the non-specificity of the 450 bp bands and revealed, respectively, 80 and 77% homology with a region in the VP1 gene of poliovirus type 1 in samples 1 and 2. This suggests that more caution should be taken in interpreting the results obtained by PCR, and that they should be confirmed by nested PCR or sequencing.

Animals↗
PubMed1979

Poliovirus replicase: a soluble enzyme able to initiate copying of poliovirus RNA.

The soluble phase of the cytoplasm of poliovirus-infected cells contains an enzymatic activity able to copy RNA without an added primer. This replicase activity has been purified 60-fold; it is absent from uninfected cells. Poly(U) polymerase activity copurifies with replicase activity. Although less pure replicase fractions copy a variety of RNAs, purer fractions respond better to poliovirus RNA than to other viral RNAs. Even the less pure fractions make a specific copy of the added template, as shown by hybridization of the product to its template RNA but not to other RNAs. Among homopolymers only poly(A)-oligo(U) was copied by the replicase; other primed homopolymer templates were inactive.

HeLa Cells↗
PubMed1997

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: II. Factors affecting detection sensitivity in a population with circulating wild poliovirus.

A basic framework for describing sensitivity of surveillance to detect poliovirus is extended from individuals to general populations (population sensitivity). Using the mathematical formulations for population sensitivity, the theoretical behavior of surveillance sensitivity under various conditions is analyzed. As a region nears the elimination of poliovirus, population sensitivity falls to a value lower than the case-to-infection ratio, regardless of the system proficiency. Also, a second stool specimen makes a substantial contribution to population sensitivity only in regions with relatively low specimen sensitivity and then only over a narrow range of population infection incidence. Estimates of the mean numbers of infected and uninfected acute flaccid paralysis cases investigated in a season are derived. These may serve as additional indicators of system operation but require the collection of 2 specimens per case.

Feces↗
PubMed1997

Eradication of wild poliovirus from the Americas: wild poliovirus surveillance--laboratory issues.

The Pan American Regional Poliomyelitis Laboratory Network, developed to support the program to eradicate indigenous wild poliovirus transmission in the Americas, included 10 laboratories, distributed in eight countries in the Americas, organized according to the diagnostic procedures they regularly performed. All laboratories isolated and typed virus in stool specimens, several did intratypic differentiation by nucleic acid probe hybridization, and 2 sequenced wild poliovirus isolates for molecular epidemiologic studies. High performance of the network was maintained through comprehensive training of virologists, continuous monitoring of laboratory performance, and prompt investigation of problems. Recommended field and laboratory procedures were regularly reviewed and revised to optimize sensitivity, specificity, and diagnostic efficiency. Close integration of field and laboratory surveillance was achieved through frequent meetings between virologists and epidemiologists, effective communication of program priorities, and the distribution of weekly surveillance reports.

Americas↗
PubMed1998

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents.

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.

Adolescent↗
PubMed1978

Isoelectric points of polypeptides of standard poliovirus particles of different serological types and of empty capsids and dense particles of poliovirus type 1.

The isoelectric points of polypeptides of standard and dense poliovirus particles and of empty capsids have been determined by isoelectric focusing in urea and by two-dimensional analysis. Comparing virus strains belonging to the three serological types of poliovirus, differences in the pI of some, but not all of the structural polypeptides are found. The pI of polypeptides of dense particles and of empty capsids are identical with those of standard particles. Polypeptide VPo present in empty capsids has a pI between those of VP4 and VP2.

Capsid↗