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Vienna, Austria

Kreil T.R.,Global Pathogen Safety
Emerging Infectious Diseases | Year: 2015

Clinical evidence suggests that antibodies from reconvales- cent donors (persons who have recovered from infection) may be effective in the treatment of Ebola virus infection. Administration of this treatment to Ebola virus-infected pa tients while preventing the transmission of other pathogenic viruses may be best accomplished by use of virus-inactivat- ed reconvalescent plasma. © 2015, Centers for Disease Control and Prevention (CDC). All rights reserved. Source

Ritchie D.L.,University of Edinburgh | Gibson S.V.,University of South Alabama | Abee C.R.,University of Texas M. D. Anderson Cancer Center | Kreil T.R.,Global Pathogen Safety | And 2 more authors.
Transfusion | Year: 2016

BACKGROUND Four secondary transmissions of variant Creutzfeldt-Jakob disease (vCJD) infectivity have been associated with the transfusion of nonleukoreduced red blood cells collected from vCJD patients during the asymptomatic phase of the disease. Establishing efficient experimental models for assessing the risk of future transmissions of vCJD infectivity via blood transfusion is of paramount importance in view of a study of archived appendix samples in which the prevalence of asymptomatic vCJD infection in the United Kingdom was estimated at approximately 1 in 2000 of the population. In this study, we investigated transmission of vCJD and sporadic CJD (sCJD) infectivity from blood using the squirrel monkey, which is highly susceptible to experimental challenge with human prion disease. STUDY DESIGN AND METHODS Whole blood collected from vCJD- and sCJD-infected squirrel monkeys was transfused at multiple time points into recipient squirrel monkeys. Blood recipients were euthanized approximately 7 years after their first blood transfusion. RESULTS No clinical or pathologic signs of a prion disease were observed in either the sCJD- or the vCJD-transfused monkeys, and immunohistochemistry and biochemical investigations showed no PrPTSE in central nervous system or lymphoreticular tissues. Similarly, monkeys inoculated intracerebrally (IC) and intravenously (IV) with either buffy coat or plasma from vCJD and sCJD patients failed to develop disease. However, white blood cells from a chimpanzee-passaged strain of human Gerstmann-Sträussler-Scheinker (GSS) disease transmitted autopsy-proven disease to two IC-inoculated monkeys after incubation periods of 34 and 39 months. CONCLUSION Blood transmits GSS but not sCJD or vCJD infectivity to IC- or IV-inoculated squirrel monkeys within a 7-year observation period. © 2015 AABB. Source

Hessel A.,Vaccine RandD | Savidis-Dacho H.,Pharmacology | Coulibaly S.,Pharmacology | Portsmouth D.,Vaccine RandD | And 7 more authors.
PLoS ONE | Year: 2014

Background: The availability of a universal influenza vaccine able to induce broad cross-reactive immune responses against diverse influenza viruses would provide an alternative to currently available strain-specific vaccines. We evaluated the ability of vectors based on modified vaccinia virus Ankara (MVA) expressing conserved influenza proteins to protect mice against lethal challenge with multiple influenza subtypes. Methods: Mice were immunized with MVA vectors expressing H5N1-derived nucleoprotein (NP), the stem region of hemagglutinin (HA), matrix proteins 1 and 2 (M1 and M2), the viral polymerase basic protein 1 (PB1), or the HA stem fused to a quadrivalent matrix protein 2 extracellular domain (M2e). Immunized mice were challenged with lethal doses of H5N1, H7N1 or H9N2 virus and monitored for disease symptoms and weight loss. To investigate the influence of previous exposure to influenza virus on protective immune responses induced by conserved influenza proteins, mice were infected with pandemic H1N1 virus (H1N1pdm09) prior to immunization and subsequently challenged with H5N1 virus. Antibody and T cell responses were assessed by ELISA and flow cytometry, respectively. Results: MVA vectors expressing NP alone, or co-expressed with other conserved influenza proteins, protected mice against lethal challenge with H5N1, H7N1 or H9N2 virus. Pre-exposure to H1N1pdm09 increased protective efficacy against lethal H5N1 challenge. None of the other conserved influenza proteins provided significant levels of protection against lethal challenge. NP-expressing vectors induced high numbers of influenza-specific CD4+ and CD8+ T cells and high titer influenzaspecific antibody responses. Higher influenza-specific CD4+ T cell responses and NP-specific CD8+ T cell responses were associated with increased protective efficacy. Conclusions: MVA vectors expressing influenza NP protect mice against lethal challenge with H5N1, H7N1 and H9N2 viruses by a mechanism involving influenza-specific CD4+ and CD8+ T cell responses. © 2014 Hessel et al. Source

Planitzer C.B.,Global Pathogen Safety | Farcet M.R.,Global Pathogen Safety | Schiff R.I.,Clinical Affairs | Ochs H.D.,University of Washington | Kreil T.R.,Global Pathogen Safety
Journal of Medical Virology | Year: 2011

Replacement therapy using intravenous immunoglobulin (IVIG) preparations in people with antibody deficiencies is effective in preventing the majority of common bacterial and viral infections, yet echovirus break-through infections have occurred. Currently, only limited information on neutralization capacity variability of individual IVIG lots against the different echovirus serotypes is available. Infectivity assays were established for the most prevalent echovirus serotypes (E 9, E 11, E 13, and E 30) circulating in the United States (US) and the European Union (EU). The echovirus serotype-specific neutralization titers of 41 IVIG lots manufactured from either whole blood (Recovered) or collected by apheresis (Source) and from either the US or EU, were determined. Significantly higher (P < 0.0001) neutralization titers against E 11 and E 30 were found in IVIG lots manufactured from US Source plasma compared to US Recovered plasma. Geographically, IVIG lots made from US plasma contained significantly (P < 0.0001) higher neutralization titers against E 9 and E 11 than lots manufactured from EU plasma, whereas lots made from EU plasma showed significantly higher neutralization of E 30. To conclude, IVIG lots differ in their neutralizing antibody content against different echovirus serotypes, depending on plasma collection practices and geographic origin. Based on these results, an informed choice in selecting IVIG lots with the highest available neutralization titer against the specific echovirus serotype would seem to be beneficial during treatment of break-through infections. © 2010 Wiley-Liss, Inc. Source

Berting A.,Global Pathogen Safety | Farcet M.R.,Global Pathogen Safety | Kreil T.R.,Global Pathogen Safety
Biotechnology and Bioengineering | Year: 2010

Biopharmaceuticals are of increasing importance in the treatment of a variety of diseases. A remaining concern associated with their production is the potential introduction of adventitious agents into their manufacturing process, which may compromise the pathogen safety of a product and potentially cause stock-out situations for important medical supplies. To ensure the safety of biological therapeutics, regulatory guidance requires adventitious agent testing (AAT) of the bulk harvest. AAT is a deliberately promiscuous assay procedure which has been developed to indicate, ideally, the presence of any viral contaminant. One of the most important cell lines used in the production of biopharmaceuticals is Chinese hamster ovary (CHO) cells and while viral infections of CHO cells have occurred, a systematic screen of their virus susceptibility has never been published. We investigated the susceptibility of CHO cells to infection by 14 different viruses, including members of 12 families and representatives or the very species that were implicated in previously reported production cell infections. Based on our results, four different infection outcomes were distinguished, based on the possible combinations of the two factors (i) the induction, or not, of a cytopathic effect and (ii) the ability, or not, to replicate in CHO cells. Our results demonstrate that the current AAT is effective for the detection of viruses which are able to replicate in CHO cells. Due to the restricted virus susceptibility of CHO cells and the routine AAT of bulk harvests, our results provide re-assurance for the very high safety margins of CHO cell-derived biopharmaceuticals. © 2010 Wiley Periodicals, Inc. Source

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