Publications by authors named "Eugenia Dragunsky"

The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks.

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Background: Development of anti-poliovirus therapies to complement vaccination is an urgent priority. A number of antiviral drugs are in development. Recently we have developed human monoclonal antibodies that could be used for treatment of chronically infected individuals and emergency response to potential reappearance of polioviruses after eradication.

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Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles.

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MicroRNA expression appears to capture the process of neoplastic development in vitro in the VERO line of African green monkey kidney (AGMK) cells (Teferedegne et al. PLoS One 2010;5(12):e14416). In that study, specific miRNA signatures were correlated with the transition, during serial tissue-culture passage, of low-density passaged 10-87 VERO cells from a non-tumorigenic phenotype at passage (p) 148 to a tumorigenic phenotype at p256.

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Unlabelled: Few drugs targeting picornaviruses are available, making the discovery of antivirals a high priority. Here, we identified and characterized three compounds from a library of kinase inhibitors that block replication of poliovirus, coxsackievirus B3, and encephalomyocarditis virus. Using an in vitro translation-replication system, we showed that these drugs inhibit different stages of the poliovirus life cycle.

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Background: The National Research Council has recommended development of polio antiviral drugs to assist in management of outbreaks and to mitigate adverse consequences of vaccination. V-073 is a small molecule poliovirus capsid inhibitor that is being developed for these purposes. Antiviral use raises the potential of treatment-emergent resistance.

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Immunization of mice with inactivated polio vaccine (IPV) with concurrent dosing of poliovirus antiviral V-073 showed no detrimental impact on the elicitation of serum-neutralizing antibodies. A strategy involving coadministration of antiviral V-073 and IPV can be considered for the management of poliovirus incidents.

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Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus.

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A blocking-ELISA procedure was used to quantify antibodies in sera of humans immunized with poliovirus vaccines. Titers determined by this method demonstrated an excellent correlation with the results of neutralization test. Testing of serum potency with a panel of type 1 poliovirus strains altered antigenically was used to evaluate the composition of polyclonal sera with respect to the epitope specificity of constituent antibodies.

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Proteasome activity is an important part of viral replication. In this study, we examined the effect of proteasome inhibitors on the replication of vesicular stomatitis virus (VSV) and poliovirus. We found that the proteasome inhibitors significantly suppressed VSV protein synthesis, virus accumulation, and protected infected cells from toxic effect of VSV replication.

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Recently, we developed and optimized a new method for the evaluation of the protective properties of serotype 2 inactivated poliovirus vaccines (IPV). The method is based on the immunization and subsequent challenge of transgenic (Tg) mice susceptible to poliovirus. We describe a similar method for the assessment of the protectiveness of serotype 1 IPV and demonstrate that experimental IPV produced from attenuated Sabin strain (sIPV) of serotype 1 poliovirus induced serum neutralizing antibodies, immunoglobulin (Ig) G, IgM, and salivary IgA at titers comparable to those induced by conventional IPV (cIPV) produced from the wild-type Mahoney strain.

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Purpose: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis.

Experimental Design: To evaluate for toxicity, PVS-RIPO was administered into the spinal cord of transgenic mice that express the human poliovirus receptor, CD155, and into the intrathecal space of athymic rats without tumor. To evaluate efficacy, two different doses of PVS-RIPO were administered intrathecally 3 days after athymic rats were inoculated intrathecally with an aggressive human glioblastoma multiforme xenograft.

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1,25-Dihydroxyvitamin D3 (DHVD3) coadministered with monovalent inactivated poliovirus vaccine (IPV) of all 3 serotypes significantly enhances antipoliovirus systemic and mucosal immunity in mice. Although serum immunoglobulin G antibodies are significantly higher in serotypes 2 and 3, and although salivary immunoglobulin A is significantly increased in serotypes 1 and 3, DHVD3 had the most dramatic effect on the level of neutralizing serum antibodies of all 3 IPV serotypes. These findings suggest a possible use of vitamin D3 as an adjuvant for currently used and proposed new Sabin IPVs.

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Sabin strains of poliovirus used in the manufacture of oral poliovirus vaccine (OPV) are prone to genetic variations that occur during growth in cell cultures and the organisms of vaccine recipients. Such derivative viruses often have increased neurovirulence and transmissibility, and in some cases they can reestablish chains of transmission in human populations. Monitoring for vaccine-derived polioviruses is an important part of the worldwide campaign to eradicate poliomyelitis.

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This review describes several enzyme-linked immunosorbent assay (ELISA) techniques proposed to replace the neutralization test for detecting neutralization-relevant antibodies to polioviruses in recipients of inactivated poliovirus vaccine and oral poliovirus vaccine, and for seroepidemiologic studies. Comparisons of results from ELISA and the neutralization test suggest that ELISA variants, based on the principle of blocking or binding inhibition that emulate the neutralization test, might offer an alternative to the neutralization test. However, to replace the neutralization test with ELISA would first require extensive studies with very large numbers of serum samples, including sera having low titers of neutralizing antibodies, in order to obtain reliable and statistically sound validation.

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This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to three types of Sabin strains of poliovirus in saliva taken from 70 children aged 6-7 years vaccinated with a full course of oral poliovirus vaccine (OPV). Of the three ELISA methods (conventional IgA ELISA and two new methods described in this communication, the alpha-capture ELISA and Inhibition ELISA), alpha-capture ELISA demonstrated the highest sensitivity, with all saliva samples testing positive for Sabin poliovirus strains specific IgA antibodies of 1-3 types. Of 62 available alpha-capture ELISA positive saliva samples, all were also positive by the inhibition ELISA, and a significant correlation was found between the results.

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An improved ELISA test for determination of potency of Inactivated Poliovirus Vaccine (IPV) is proposed. The method is based on the use of IgG purified from immune rabbit serum conjugated with biotin. Optimized and validated materials for the test can be stored for a long time in the form of ready-to-use kits.

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An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice.

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Two approaches based on hybridization of viral probes with oligonucleotide microarrays were developed for rapid analysis of genetic variations during microevolution of RNA viruses. Microarray analysis of viral recombination and microarray for resequencing and heterogeneity analysis were able to generate instant genetic maps of vaccine-derived polioviruses (VDPVs) and reveal the degree of their evolutionary divergence. Unlike conventional methods based on cDNA sequencing and restriction fragment length polymorphism, the microarray approaches are better suited for analysis of heterogeneous populations and mixtures of different strains.

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Objective: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV).

Methods: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice.

Findings: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians.

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