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Biologicals : Journal of the... Jun 1998Virus inactivation by cold treatment with beta-propiolactone (BPL) was investigated in human cryo poor plasma and purified IgG concentrates spiked with relevant human...
Virus inactivation by cold treatment with beta-propiolactone (BPL) was investigated in human cryo poor plasma and purified IgG concentrates spiked with relevant human viruses or appropriate animal model viruses. The samples were treated with 0.1 or 0.25% BPL for 300 or 480 min, respectively. Residual infectivity was determined by standard microtitration assays on tissue culture cells. The inactivation of all viruses tested was more effective in IgG than in plasma. IgG: R1=4-5.5 log10 for vesicular stomatitis virus (VSV). Semliki Forest virus (SFV), bovine virus diarrhoea virus (BVDV), murine encephalomyelitis virus (MEV), feline calicivirus (FVC), suid parvovirus (PPV), simian virus 40 (SV40); R1=2-4 log10 for suid herpesvirus type 1 (SHV-1), bovine herpesvirus type 1 (BHV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency virus (SIVagm3). Plasma: R1=3-5 log10 for VSV, SFV, BVDV, SHV-1, MEV:R1=0-3 log10 for HIV-1, SIVagm3 BHV-1, FCV, PPV, SV40. After addition of SIVagm3, HIV-2, and PPV to plasma or IgG, spontaneous inactivation without further addition of BPL was observed. These results demonstrate that treatment with BPL has a limited capacity to inactivate viruses. Different inactivation kinetics were observed in plasma and IgG concentrates. Therefore, virus inactivation by BPL must be tested for individual blood products independently and should not be extrapolated from other model systems.
Topics: Animals; Cats; Cattle; Cell Line; Disinfectants; Humans; Immunoglobulin G; Kinetics; Models, Biological; Plasma; Propiolactone; Safety; Virus Diseases; Viruses
PubMed: 9811521
DOI: 10.1006/biol.1998.0125 -
Journal of Chromatography Jul 1972
Topics: Butyrates; Chromatography, Gas; Hydrogen-Ion Concentration; Hydrolysis; Lactones; Methods; Propionates; Rabies Vaccines; Time Factors
PubMed: 5050707
DOI: 10.1016/s0021-9673(01)91065-9 -
Biologicals : Journal of the... Sep 1995Inactivating treatments for viruses such as pasteurization or alkylation by beta-propiolactone or binary ethyleneimine were tested for their capacity to modify nucleic...
Inactivating treatments for viruses such as pasteurization or alkylation by beta-propiolactone or binary ethyleneimine were tested for their capacity to modify nucleic acids. The modification of a nucleic acid was measured as the decrease in spot intensity in Southern blots after polymerase chain reaction (PCR) amplification. The inactivating treatments were applied to cellular and viral genomic material from a human lymphoblastoid cell line immortalized by Epstein Barr Virus (EBV), which produced a monoclonal antibody. Pasteurization did not modify the ability to amplify and detect cellular or viral DNA. Binary ethyleneimine strongly reduced the amount of detectable DNA and beta-propiolactone under particular conditions of incubation abolished all trace of DNA.
Topics: Alkylating Agents; Aziridines; Base Sequence; Cell Line; DNA; DNA Damage; DNA Primers; DNA Probes; Heating; Herpesvirus 4, Human; Humans; Molecular Sequence Data; Polymerase Chain Reaction; Propiolactone; Tumor Cells, Cultured
PubMed: 8527120
DOI: 10.1006/biol.1995.0035 -
Applied Microbiology Jul 1961Studies were made comparing the toxicity of beta-propiolactone (BPL) for mammalian (mouse) cells in vitro and for mice and for Venezuelan equine encephalomyelitis (VEE)...
Studies were made comparing the toxicity of beta-propiolactone (BPL) for mammalian (mouse) cells in vitro and for mice and for Venezuelan equine encephalomyelitis (VEE) virus which is highly cytopathogenic for each. The mammalian cells grown in tissue culture were found to be adversely affected by BPL in concentrations ranging from 0.001 to 0.1 mg/ml of supernatant fluid. The difference in response was influenced by the menstruum in which the BPL was suspended and the difference in cell types tested. Tenfold less BPL appeared to be required to destroy the cells when it was suspended in a balanced salt solution than when it was suspended in protein-containing solutions such as beef heart infusion broth or medium 199 plus 20% horse serum. Secondary embryonic mouse lung cells seemed slightly more adversely affected by BPL than the established embryonic lung or L cells. BPL given to mice by intranasal instillation and by intracerebral injection was lethal to half of the animals within 2 days at doses of 0.31 and 0.39 mg, respectively. Higher concentrations of BPL were required to rapidly inactivate the virus in vitro than were required to kill mice or to cause a toxic effect on cells in culture. It required 10 mg/ml of BPL to completely inactivate a high-titered VEE virus preparation in 5 min and 1 mg/ml to inactivate most, but not all, of the virus in 15 min. A concentration of 0.1 mg/ml of BPL had only a slight effect on the virus after a period as long as 60 min. Evidence is presented indicating that simultaneous inactivation of all of the properties of the VEE virus particles by BPL aerosols did not occur at the same time but that, after treatment, the virus possessed a limited ability to immunize mice despite a loss in infectivity.
Topics: Animals; Cattle; Cell Culture Techniques; Encephalitis Virus, Venezuelan Equine; Encephalomyelitis; Encephalomyelitis, Equine; Encephalomyelitis, Venezuelan Equine; Horses; Immunologic Tests; L Cells; Lactones; Mice; Propiolactone; Tissue Culture Techniques; Viruses
PubMed: 13712596
DOI: 10.1128/am.9.4.278-282.1961 -
Biomeditsinskaia Khimiia Nov 2023Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not... (Review)
Review
Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the antigenic determinants of the inactivated particles and require additional purification stages. The most promising platforms for creating vaccines are based on pseudoviruses, i.e., viruses that have completely preserved the outer shell (capsid), while losing the ability to reproduce owing to the destruction of the genome. The irradiation of viruses with electron beam is the optimal way to create pseudoviral particles. In this review, with the example of the poliovirus, the main algorithms that can be applied to characterize pseudoviral particles functionally and structurally in the process of creating a vaccine preparation are presented. These algorithms are, namely, the analysis of the degree of genome destruction and coimmunogenicity. The structure of the poliovirus and methods of its inactivation are considered. Methods for assessing residual infectivity and immunogenicity are proposed for the functional characterization of pseudoviruses. Genome integrity analysis approaches, atomic force and electron microscopy, surface plasmon resonance, and bioelectrochemical methods are crucial to structural characterization of the pseudovirus particles.
Topics: Humans; Poliovirus; Vaccines; Formaldehyde; Propiolactone; Poliomyelitis
PubMed: 37937429
DOI: 10.18097/PBMC20236905253 -
Thrombosis Research Oct 1982The association of viral hepatitis, type B, with the use of prothrombin complex concentrates (PPSB) has been well documented. PPSB prepared from cold-sterilized plasma...
The association of viral hepatitis, type B, with the use of prothrombin complex concentrates (PPSB) has been well documented. PPSB prepared from cold-sterilized plasma (beta-propiolactone treated and UV irradiated) has been shown not to induce hepatitis in chimpanzees. 500 U of cold-sterilized PPSB were infused into 5 healthy male volunteers. Previous to, and up to 6 months after, PPSB-application in addition to careful clinical investigations, the following hepatitis parameters were determined: SGOT, SGPT, y-GT, alkaline phosphatase, total serum bilirubin, HBsAg, HBcAb and HBsAb. On the basis of all of the above parameters there was no indication of induction of viral hepatitis following the application of PPSB prepared from beta-propiolactone/UV treated plasma.
Topics: Adult; Animals; Cold Temperature; Factor IX; Hepatitis B; Hepatitis B Surface Antigens; Humans; Lactones; Male; Middle Aged; Propiolactone; Prothrombin; Sterilization; Ultraviolet Rays
PubMed: 7157232
DOI: 10.1016/0049-3848(82)90035-4 -
Journal of Pharmaceutical Analysis Dec 2018A simple method was established for the determination of -propiolactone (BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry (GC-MS). The...
A simple method was established for the determination of -propiolactone (BPL) in human inactivated rabies vaccine by gas chromatography-mass spectrometry (GC-MS). The determination was performed on an Agilent HP-INNOWAX (30 m × 0.32 mm i.d., 0.25 µm) capillary column at the temperature of 80 °C. Electrospray ionization (ESI) was used by selective ion detection at 42. The temperature for ESI source and inlet was set at 230 °C and 200 °C, respectively. Helium was used as the carrier gas at a flow rate of 25.1 mL/min. The total run time was 8 min. Acetonitrile and other components in the sample did not interfere with the determination of BPL. The results showed good linearity of BPL in the range of 0.50-10.01 μg/mL, with the limit of detection and the limit of quantification of 0.015 μg/mL and 0.050 μg/mL, respectively. Satisfactory precision was achieved for the current developed method. The method was applied to detect 6 batches of vaccine samples, and the results indicated that the target analyte BPL was present in three batches of unpurified samples, but was not detected in the purified samples, indicating the test samples were qualified. The established method was proved to be simple, versatile and sensitive, which can meet the requirements of quality control of BPL in human inactivated rabies vaccine.
PubMed: 30595943
DOI: 10.1016/j.jpha.2018.06.003 -
Journal of the American Medical... Apr 1960
Topics: Humans; Lactones; Propiolactone; Sterilization; Sterilization, Reproductive
PubMed: 13792743
DOI: 10.1001/jama.1960.03020160031006 -
Research in Experimental Medicine.... Sep 1978Dog IgG was produced by fractionation procedures used for the production of clinically used i.v. gammaglobulins. Chemical modification of dog IgG was done by pepsin or...
Elimination and organ distribution of intravenously administered allogeneic and xenogeneic IgG modifications. (Standard IgG, F (ab)2-fragments and beta-propiolactone treated IgG) in dogs.
Dog IgG was produced by fractionation procedures used for the production of clinically used i.v. gammaglobulins. Chemical modification of dog IgG was done by pepsin or beta-propiolactone treatment. The intravascular half-life of beta-propiolactone IgG was 8.5 +/- 2.1 days compared to 4.5 +/- 1.6 days of pepsin treated IgG. Tissue concentrations of radioactive labelled beta-propiolactone IgG were generally higher than of pepsin digested IgG. Pepsin treated Igg was degraded to a significantly higher extent (26% of the administered radioactivity was bound to fragments smaller than 6000 MW after three days) than beta-propiolactone IgG (9% fragments after the same interval, P less than 0.001). It is concluded that the short intravascular half-life of pepsin IgG cannot be explained by increased extravascular filling, but is due to rapid degradation and excretion via the kidneys. There was no obvious difference in elimination and organ distribution between standard and beta-propiolactone IgG.
Topics: Animals; Dogs; Female; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Metabolic Clearance Rate; Molecular Weight; Pepsin A; Propiolactone; Species Specificity; Tissue Distribution
PubMed: 364571
DOI: 10.1007/BF01851492 -
Chemico-biological Interactions Mar 1981Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was... (Comparative Study)
Comparative Study
Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was 50--100 times more reactive with all the nucleophiles than beta-butyrolactone whereas gamma-butyrolactone was completely inactive. The rate of alkylation by the lactones was guanosine greater than RNA = denatured DNA greater than double-stranded DNA. The type of the adducts formed were characterized by fluorescence and ultraviolet spectroscopy. Similar alkylation products were formed by the two lactones. The main sites alkylated were N-1 at adenosine, N-3 at cytidine and N-7 at guanosine. The results suggest that the carcinogenic potency of the lactones correlates with their reactivity rather than with specificity of the adducts formed.
Topics: 4-Butyrolactone; Alkylation; Chromatography, Thin Layer; DNA; Furans; Guanosine; Lactones; Nitrobenzenes; Propiolactone; Pyridines; RNA; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet
PubMed: 6161710
DOI: 10.1016/0009-2797(81)90104-6