Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract Solvent-detergent treatment, although used routinely in plasma product processing to inactivate enveloped viruses, substantially reduces product yield from the human plasma resource.
To improve yields in plasma product manufacturing, a new viral reduction process has been developed using the fatty acid caprylate. As licensure of plasma products warrants thorough evaluation of pathogen reduction capabilities, the present study examined susceptibility of enveloped viruses to inactivation by caprylate in protein solutions with varied pH and temperature.
Caprylate-mediated inactivation of BVDV was not noticeably affected by temperature within the range chosen manufacturing the immunoglobulin product. Full text links Read article at publisher's site DOI : References Articles referenced by this article 13 Inactivation of viruses in labile blood derivatives.
Disruption of lipid-enveloped viruses by tri n-butyl phosphate detergent combinations. Inactivation of lipid-enveloped viruses in labile blood derivatives by unsaturated fatty acids. Inactivation of lipid-enveloped viruses in proteins by caprylate. Preparation and properties of serum and plasma proteins; a system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids.
The separation of the antibodies, isoagglutinins, prothrombin, plasminogen and beta1-lipoprotein into subfractions of human plasma. Title not supplied Cavalli-Sforza Determination of adequate moisture content for efficient dry-heat viral inactivation in lyophilized factor VIII by loss on drying and by near infrared spectroscopy. Title not supplied Stecher Chemical, clinical, and immunological studies on the products of human plasma fractionation; inactivation of the virus of homologous serum hepatitis in solutions of normal human serum albumin by means of heat.
Show 3 more references 10 of Smart citations by scite. The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles. Explore citation contexts and check if this article has been supported or disputed. Evaluation of the effectiveness of the SurePure Turbulator ultraviolet-C irradiation equipment on inactivation of different enveloped and non-enveloped viruses inoculated in commercially collected liquid animal plasma.
Similar Articles To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation. Low pH, caprylate incubation as a second viral inactivation step in the manufacture of albumin.
Parametric and validation studies. Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma-derived products. Joining Europe PMC. Tools Tools overview. ORCID article claiming. Journal list. Grant finder. Not inactivated at pH 4. Inactivation below the limit of detection was not achieved.
Residual infectivity was detected in all samples. Bench controls at pH 6. Low pH inactivation was first observed by Reid et al. The data were confirmed by Kempf and others [14—16]. The data in this study confirm previous observations that incubation of IgG solutions at low pH inactivates some enveloped viruses but is less effective or even ineffective for non-enveloped viruses. Virus filtration is a simple, robust, non-destructive process that adds size exclusion to conventional virus inactivation and partitioning procedures.
The use of filtration with defined pore sizes in the nanometer range for removal of adventitious viruses is the first major advance in virus elimination since development of solvent-detergent procedures. Although BPV is 18—24 nm in size, removal of viruses smaller than the nominal pore size of the nanofilter was due to antibody-complexed virus particles [17—19].
Virus reduction is caused by different mechanisms of action, thus viruses, which might escape one procedure, are inactivated or removed by one of the subsequent procedures. Guidelines on virus validation for plasma derivatives [1,2] require a capacity of virus removal and inactivation, which can reliably remove a potential load of adventitious viruses. Virus inactivation or removal of enveloped viruses of at least 4. The virus validation results for the IGIV presented here fulfills those requirements.
In conclusion, the robust virus removal and inactivation procedures used in Biotest Pharmaceuticals IGIV production remove the enveloped and non-enveloped blood-borne viruses that are known today and has the potential to remove a broad range of emerging pathogens that might contaminate future blood supplies. Those steps are cold ethanol fractionation, nanofiltration and column chromatography [20—22] , as reported in abundance in the literature.
Consequently, the probability of a plasma donation at risk for vCJD entering a plasma pool is extremely low. In case of such an unlikely event, the production steps have sufficient capacity to remove prions. National Center for Biotechnology Information , U. Journal List Results Immunol v. Results Immunol. Published online Jan Herbert O. Dougherty d. Christopher J. Author information Article notes Copyright and License information Disclaimer.
This article has been cited by other articles in PMC. Introduction One of the most important clinical applications of intravenous immunoglobulin IGIV is to supply antibodies to patients who are antibody deficient. Materials and methods 2. Scale down The studies were performed in compliance with current guidelines [1,2] in a scaled-down version of the production process using the same parameters and controls that are used in large-scale manufacturing. Manufacturing description The manufacturing process is illustrated in Fig.
Open in a separate window. Biotest IGIV production process and virus validation conditions. Process intermediates studied Test materials for virus validation studies were produced in the Process Development Department at Biotest Pharmaceuticals Corporation, Boca Raton, Florida, USA, using a development scale manufacturing process that had been validated against the full scale manufacturing process of Biotest IGIV.
Equipment used in scale down studies Scale-down studies and virus validation studies were performed using similar equipment. Results 3. Precipitation and removal of fraction III The conditions for validation of fraction III precipitation included lowering the ethanol concentration, shortening the precipitation time and increasing the temperature.
Combination of fraction III precipitation and depth filtration of fraction III supernatant Conditions for validating the combined steps of fraction III precipitation and depth filtration Cuno of the fraction III supernatant were essentially the same as those used for each step performed separately.
Table 2 Virus removal log 10 by precipitation and removal of fraction III at different pH, followed by depth filtration. Virus pH 5. Discussion 4. Virus inactivation and removal During plasma fractionation, classes of proteins are precipitated and separated from proteins in solution by centrifugation or filtration.
References 1. Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products; WHO Technical Report series no.
Cavalli-Sforza L. Gustav Fischer; Stuttgart: Biometrie Grundzuge Biologisch-medizinischer Statistik [Biometry, the basics of biological and medical statistics] [p. Contribution to safety of immunoglobulin and albumin from virus partitioning and inactivation by cold ethanol fractionation: a data collection from Plasma Protein Therapeutics Association member companies.
Prince A. The development of virus-free labile blood derivatives—a review. The percentage of cell viability was calculated as the ratio of absorbance in treated cells compared with that in untreated controls. All experiments were performed in triplicate and repeated twice. After different time periods at RT, treated samples were diluted fold in culture medium immediately to stop the inactivation reaction, as well as to eliminate the cytotoxic effect of aldehydes in subsequent FFU assays according to the results of the MTT assay, the presence of 0.
Samples showing negative results in FFU assay were subjected to the residual infectivity test, as described in "HCV infectivity assay" As control, PBS was substituted for the aldehydes to treat the virus stocks, which were then diluted fold to infect cells in the presence of either 0.
Solutions of 0. After a gentle mixing within 1 min , treated samples were diluted fold SDS-treated samples or fold Triton X or NPtreated samples immediately in culture medium to negate the cytotoxic effect of detergents based on the MTT assay results, the presence of 0. Samples with negative FFU assay results were examined for residual infectivity.
As control, PBS was used in place of the detergents to treat the virus stocks, which were subsequently diluted either or fold to infect the HuhCD81 cells in the presence of 0. After centrifugation, the supernatants of cell lysates were diluted fold SDS-lysed samples or fold Triton X or NPlysed samples in culture medium for infectivity assays. In Fields Virology. Fifth edition. Google Scholar. Lancet Infect Dis , 9: Alter MJ: The detection, transmission, and outcome of hepatitis C virus infection.
Infect Agents Dis , 2: Infect Control Hosp Epidemiol , PubMed Article Google Scholar. Hilfenhaus J, Groner A, Nowak T, Weimer T: Analysis of human plasma products: polymerase chain reaction does not discriminate between live and inactivated viruses. Transfusion , Am J Infect Control , J Photochem Photobiol B , Vox Sang , J Virol , Science , Nat Med , Burnouf T, Radosevich M: Reducing the risk of infection from plasma products: specific preventative strategies.
Blood Rev , Schlegel A, Immelmann A, Kempf C: Virus inactivation of plasma-derived proteins by pasteurization in the presence of guanidine hydrochloride. J Virol Methods , Possible role of Dewar photoproducts in solar mutagenesis.
J Biol Chem , Fraenkel-Conrat H: Reaction of nucleic acid with formaldehyde. Biochim Biophys Acta , Jiang W, Schwendeman SP: Formaldehyde-mediated aggregation of protein antigens: comparison of untreated and formalinized model antigens. Biotechnol Bioeng , J Hosp Infect , Roberts PL, Dunkerley C: Effect of manufacturing process parameters on virus inactivation by solvent-detergent treatment in a high-purity factor IX concentrate. J Microbiol , CAS Google Scholar. Download references. We are grateful to Dr.
We also thank Dr. You can also search for this author in PubMed Google Scholar. Correspondence to Hui Zhuang or Kui Li. HZ and KL conceived the study and designed the experiments. All Authors have read and approved the final manuscript. Reprints and Permissions. Song, H. Thermal stability and inactivation of hepatitis C virus grown in cell culture.
Virol J 7, 40 Download citation. Received : 03 November Accepted : 18 February Published : 18 February Anyone you share the following link with will be able to read this content:.
Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF.
Conclusions The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. Figure 1. Full size image. Figure 2. Figure 3. Figure 4. Table 1 Effects of formaldehyde and glutaraldehyde on infectivity of HCVcc in culture medium Full size table. Table 2 Effects of formaldehyde and glutaraldehyde on infectivity of HCVcc in human serum Full size table.
Discussion In this study, a detailed analysis was conducted on the stability of HCVcc at various environmental temperatures. Conclusions In summary, results presented in the current study revealed the stability of HCVcc genotype 2a, JFH-1 strain under different temperatures and provided quantitative evidence that heat, UVC light irradiation, aldehyde formaldehyde and glutaraldehyde , and detergent treatments all can be used as effective means for inactivating HCVcc.
Viral stability assays An HCVcc stock with a titer of 2. Heat treatment An HCVcc stock in culture medium 2.
0コメント