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Journal of Biological Standardization Apr 1986The recovery of poliovirus D-antigen after virus inactivation was studied for two inactivating agents (beta-propiolactone and formalin) using the three poliovirus types... (Comparative Study)
Comparative Study
The recovery of poliovirus D-antigen after virus inactivation was studied for two inactivating agents (beta-propiolactone and formalin) using the three poliovirus types (Sabin types 1, 2 and 3). With beta-propiolactone (BPL), D-antigen recoveries were high (88, 88 and 60%, respectively) but were significantly less when formalin was used (22, 15 and 25%). beta-Propiolactone inactivated virus was purified, combined with Freund's adjuvant and used to hyperimmunize rabbits. High titres (50 000-200 000) of specific neutralizing antibody were obtained.
Topics: Animals; Antigens, Viral; Enzyme-Linked Immunosorbent Assay; Formaldehyde; Lactones; Poliovirus; Poliovirus Vaccine, Inactivated; Propiolactone; Rabbits; Vaccines, Attenuated; Virus Cultivation
PubMed: 3020055
DOI: 10.1016/0092-1157(86)90028-4 -
Analytical Chemistry Jun 2024Virus inactivation is a prerequisite for safe handling of high-risk infectious samples. β-Propiolactone (BPL) is an established reagent with proven virucidal efficacy....
Virus inactivation is a prerequisite for safe handling of high-risk infectious samples. β-Propiolactone (BPL) is an established reagent with proven virucidal efficacy. BPL primarily reacts with DNA, RNA, and amino acids. The latter may modify antigenic protein epitopes interfering with binding properties of affinity reagents such as antibodies and aptamers used in affinity proteomic screens. We investigated (i) the impact of BPL treatment on the analysis of protein levels in plasma samples using the aptamer-based affinity proteomic platform SomaScan and (ii) effects on protein detection in conditioned medium samples using the proximity extension assay-based Olink Target platform. In the former setup, BPL-treated and native plasma samples from patients with ovarian cancer ( = 12) and benign diseases ( = 12) were analyzed using the SomaScan platform. In the latter, conditioned media samples collected from cultured T cells with ( = 3) or without ( = 3) anti-CD3 antibody stimulation were analyzed using the Olink Target platform. BPL-related changes in protein detection were evaluated comparing native and BPL-treated states, simulating virus inactivation, and impact on measurable group differences was assessed. While approximately one-third of SomaScan measurements were significantly changed by the BPL treatment, a majority of antigen/aptamer interactions remained unaffected. Interaction effects of BPL treatment and disease state, potentially altering detectability of group differences, were observable for less than one percent of targets (0.6%). BPL effects on protein detection with Olink Target were also limited, affecting 3.6% of detected proteins with no observable interaction effects. Thus, effects of BPL treatment only moderately interfere with affinity proteomic detectability of differential protein expression between different experimental groups. Overall, the results prove high-throughput affinity proteomics well suited for the analysis of high-risk samples inactivated using BPL.
Topics: Humans; Proteomics; Propiolactone; Female; Biomarkers; Ovarian Neoplasms; Virus Inactivation; Aptamers, Nucleotide
PubMed: 38810147
DOI: 10.1021/acs.analchem.3c04116 -
Henry Ford Hospital Medical Bulletin Jun 1957
Topics: Anti-Infective Agents, Local; Propiolactone; Sterilization; Sterilization, Reproductive; Transplantation
PubMed: 13438439
DOI: No ID Found -
Journal of Virological Methods Sep 2016Beta-propiolactone (BPL) is used as an inactivating reagent for influenza virus in a number of countries. However, the treatment of viruses with BPL occasionally results...
Beta-propiolactone (BPL) is used as an inactivating reagent for influenza virus in a number of countries. However, the treatment of viruses with BPL occasionally results in a decrease in the hemagglutinin (HA) titer, which complicates vaccine development. In the present study, we examined the biological and biochemical characteristics of human H1N1 and H3N2 viruses treated with BPL, and developed an inactivation method for BPL-sensitive viruses. A significant decrease in HA titer was detected in the H3N2 viruses examined. The decrease in the pH of the virus fluid was not associated with the decreased HA titer, indicating that the decrease in HA titer for the H3N2 virus is the result of the direct effect of BPL. Excessive modification of M1 by BPL and loss of virion diameter were observed in 0.1% BPL-treated H3N2 virus. Taken together, these results suggest that the BPL sensitivity of H3N2 virus results from disruption of the virion. By contrast, the H3N2 virus was successfully inactivated by 0.02% BPL without a significant decrease in the HA titer or disruption of virion structure. Furthermore, we found that the 0.02% BPL in the virion preparation was hydrolyzed successfully by incubation at 37°C for 7h. Thus, mild treatment with a low concentration of BPL enabled us to inactivate the H3N2 virus.
Topics: Animals; Dogs; Humans; Hydrolysis; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Madin Darby Canine Kidney Cells; Propiolactone; Virion; Virus Inactivation
PubMed: 27142111
DOI: 10.1016/j.jviromet.2016.04.013 -
Acta Pathologica Et Microbiologica... Apr 1975The effect of beta-propiolactone (BPL) on the infectivity and haemagglutinating properties of BK virus was studied. No virus multiplication was observed when Vero cell...
The effect of beta-propiolactone (BPL) on the infectivity and haemagglutinating properties of BK virus was studied. No virus multiplication was observed when Vero cell cultures were inoculated with virus treated with 0.1 per cent or higher concentration of BPL. On the other hand, treatment of BK virus with 0.1 per cent or lower concentration of BPL had no apparent effect on viral haemagglutinin. BPL at a concentration of 0.1 per cent could therefore be used to prepare BK virus haemagglutinin which contains little or no infectious virus. Inactivated haemagglutinin seems to be somewhat labile against freezing and thawing, but storage at 4 degrees C had no effect on it. Identical haemagglutination inhibiting antibody titres were obtained when human sera were tested with standard haemagglutinin or with haemagglutinin inactivated with BPL.
Topics: Agglutinins; BK Virus; Depression, Chemical; Drug Resistance, Microbial; Hemagglutinins; Humans; Lactones; Polyomavirus; Propiolactone
PubMed: 168727
DOI: 10.1111/j.1699-0463.1975.tb00084.x -
Vaccine Jul 2018During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1...
During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1 vaccines. However, preparation of multiple vaccines from live H5N1 HPAI viruses is difficult and economically not feasible representing a challenge for pandemic preparedness. Here we evaluated a novel multi-clade recombinant H5N1 virus-like particle (VLP) design, in which H5 hemagglutinins (HA) and N1 neuraminidase (NA) derived from four distinct clades of H5N1 virus were co-localized within the VLP structure. The multi-clade H5N1 VLPs were prepared by using a recombinant baculovirus expression system and evaluated for functional hemagglutination and neuraminidase enzyme activities, particle size and morphology, as well as for the presence of baculovirus in the purified VLP preparations. To remove residual baculovirus, VLP preparations were treated with beta-propiolactone (BPL). Immunogenicity and efficacy of multi-clade H5N1 VLPs were determined in an experimental ferret H5N1 HPAI challenge model, to ascertain the effect of BPL on immunogenicity and protective efficacy against lethal challenge. Although treatment with BPL reduced immunogenicity of VLPs, all vaccinated ferrets were protected from lethal challenge with influenza A/VietNam/1203/2004 (H5N1) HPAI virus, indicating that multi-clade VLP preparations treated with BPL represent a potential approach for pandemic preparedness vaccines.
Topics: Animals; Disinfectants; Ferrets; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Male; Orthomyxoviridae Infections; Propiolactone; Survival Analysis; Vaccines, Virus-Like Particle
PubMed: 29885769
DOI: 10.1016/j.vaccine.2018.05.092 -
Science (New York, N.Y.) Nov 1951
Topics: Genetics; Humans; Mutation; Propiolactone
PubMed: 14892770
DOI: 10.1126/science.114.2967.490 -
Proteomics Dec 2013Inactivation of intact influenza viruses using formaldehyde or β-propiolactone (BPL) is essential for vaccine production and safety. The extent of chemical...
Inactivation of intact influenza viruses using formaldehyde or β-propiolactone (BPL) is essential for vaccine production and safety. The extent of chemical modifications of such reagents on viral proteins needs to be extensively investigated to better control the reactions and quality of vaccines. We have evaluated the effect of BPL inactivation on two candidate re-assortant vaccines (NIBRG-121xp and NYMC-X181A) derived from A/California/07/2009 pandemic influenza viruses using high-resolution FT-ICR MS-based proteomic approaches. We report here an ultra performance LC MS/MS method for determining full-length protein sequences of hemagglutinin and neuraminidase through protein delipidation, various enzymatic digestions, and subsequent mass spectrometric analyses of the proteolytic peptides. We also demonstrate the ability to reliably identify hundreds of unique sites modified by propiolactone on the surface of glycoprotein antigens. The location of these modifications correlated with changes to protein folding, conformation, and stability, but demonstrated no effect on protein disulfide linkages. In some cases, these modifications resulted in suppression of protein function, an effect that correlated with the degree of change of the modified amino acids' side chain length and polarity.
Topics: Amino Acid Sequence; Antigens, Viral; Cysteine; Hemagglutinins; Influenza Vaccines; Neuraminidase; Nucleocapsid Proteins; Polysaccharides; Propiolactone; RNA-Binding Proteins; Tandem Mass Spectrometry; Viral Core Proteins; Viral Proteins; Virus Inactivation
PubMed: 24123778
DOI: 10.1002/pmic.201300096 -
Lancet (London, England) Oct 1980
Topics: Animals; Drug Resistance, Microbial; Hepatitis B virus; Humans; Lactones; Pan troglodytes; Propiolactone; Ultraviolet Rays; Virulence
PubMed: 6107566
DOI: 10.1016/s0140-6736(80)92074-7 -
Reviews of Infectious Diseases 1983The efficacy of combined beta-propiolactone/ultraviolet irradiation (betaPL/UV) for inactivation of hepatitis B virus in labile blood derivatives has been reviewed. The...
The efficacy of combined beta-propiolactone/ultraviolet irradiation (betaPL/UV) for inactivation of hepatitis B virus in labile blood derivatives has been reviewed. The initial evaluations of these procedures were hampered by inadequate process control that resulted in excessive protein denaturation; furthermore, adequate evaluation of process efficacy for virus inactivation was prevented by the absence of titered hepatitis virus stocks, the lack of an animal model, and the failure to carry out controlled trials. Finally, it was not appreciated that the power of these procedures lay especially in their use in combination. These deficits have now been remedied. To permit quantitation of process efficacy, a regression analysis of the relation between virus dose and incubation period in chimpanzees has been carried out. This has provided a means of estimating virus titer and determining the accuracy of such estimates. The most recent data suggest that betaPL/UV can reduce the titer of hepatitis B virus about 10 million fold (10(-7)). The process efficacy for betaPL/UV followed by the special adsorption procedures used in preparation of a stabilized human serum containing most human serum proteins except for factor VIII, the factor IX complex, fibrinogen, and the lipoproteins was estimated as a 10(8)-fold reduction in virus titer. This degree of virus inactivation should be more than sufficient to sterilize the amounts of hepatitis B virus that could be expected in pooled human plasma that has been screened for hepatitis B surface antigen. Preliminary data also suggest that the betaPL/UV procedure effectively inactivates non-A, non-B hepatitis virus(es).
Topics: Animals; Blood; Blood Transfusion; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Lactones; Male; Pan troglodytes; Propiolactone; Ultraviolet Rays
PubMed: 6828813
DOI: 10.1093/clinids/5.1.92