Inactivation of Lipid Enveloped Viruses by Octanoic Acid Treatment of Immunoglobulin Solution

Dichtelmüller, H.; Rudnick, Dorothea; Kloft, M.

doi:10.1006/biol.2002.0332

Cited by 52 publications

(31 citation statements)

References 3 publications

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“…The technique relies on caprylic (octanoic) acid precipitation of non-Ig molecules [14,15]. Caprylic acid is already used to prepare licensed IgG or IgM preparations from precipitates II+III [16,17], II [18], or III [18]; 5%-pH 5.5 caprylic acid precipitation is also used to produce horse plasma-derived therapeutic antivenom immunoglobulins [19,20], and this process may become an alternative to chromatography for monoclonal antibodies production [21]. …”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, manufacturing processes should include one or two dedicated viral inactivation steps, a major tripod of viral safety [30,32]. Caprylic acid treatment is known to be a robust viral reduction treatment for both human [16,18,33] and horse-derived IgG [34,35]. Our study confirms that at the concentration and pH used in this work, this is highly effective against lipid-enveloped viruses, as > 4 log of HIV, BVDV and PRV were inactivated within 15 minutes of treatment.…”

Section: Discussionmentioning

confidence: 99%

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Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

El‐Ekiaby¹,

Vargas

Moussa

et al. 2015

PLoS Negl Trop Dis

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BackgroundImmunoglobulin G (IgG) is an essential plasma-derived medicine that is lacking in developing countries. IgG shortages leave immunodeficient patients without treatment, exposing them to devastating recurrent infections from local pathogens. A simple and practical method for producing IgG from normal or convalescent plasma collected in developing countries is needed to provide better, faster access to IgG for patients in need.Methodology/Principal FindingsIgG was purified from 10 consecutive minipools of 20 plasma donations collected in Egypt using single-use equipment. Plasma donations in their collection bags were subjected to 5%-pH5.5 caprylic acid treatment for 90 min at 31°C, and centrifuged to remove the precipitate. Supernatants were pooled, then dialyzed and concentrated using a commercial disposable hemodialyzer. The final preparation was filtered online by gravity, aseptically dispensed into storage transfusion bags, and frozen at <-20°C. The resulting preparation had a mean protein content of 60.5 g/L, 90.2% immunoglobulins, including 83.2% IgG, 12.4% IgA, and 4.4% IgM, and residual albumin. There was fourfold to sixfold enrichment of anti-hepatitis B and anti-rubella antibodies. Analyses of aggregates (<3%), prekallicrein (5-7 IU/mL), plasmin (26.3 mU/mL), thrombin (2.5 mU/mL), thrombin-like activity (0.011 U/g), thrombin generation capacity (< 223 nM), and Factor XI (<0.01 U/mL) activity, Factor XI/XIa antigen (2.4 ng/g) endotoxin (<0.5 EU/mL), and general safety test in rats showed the in vitro safety profile. Viral validation revealed >5 logs reduction of HIV, BVDV, and PRV infectivity in less than 15 min of caprylic acid treatment.Conclusions/Significance90% pure, virally-inactivated immunoglobulins can be prepared from plasma minipools using simple disposable equipment and bag systems. This easy-to-implement process could be used to produce immunoglobulins from local plasma in developing countries to treat immunodeficient patients. It is also relevant for preparing hyperimmune IgG from convalescent plasma during infectious outbreaks such as the current Ebola virus episode.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

El‐Ekiaby¹,

Vargas

Moussa

et al. 2015

PLoS Negl Trop Dis

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“…Caprylic acid could participate in bacteria cell growth inhibition (Skrivanová et al, 2008) and can be used as antimicrobial food additive (Viegas and Sá-Correia, 1995;Nair et al, 2005). This acid is also used in immunoglobulin purification and has antiviral activity (Dichtelmü ller et al, 2002). Capric acid, naturally present in bovine, human milk and in plant oils has potential pharmacological importance (Maher et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Two modes of fatty acid binding to bovine β‐lactoglobulin—crystallographic and spectroscopic studies

Loch¹,

Polit²,

Górecki³

et al. 2010

J of Molecular Recognition

108

104

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Lactoglobulin is a natural protein present in bovine milk and common component of human diet, known for binding with high affinity wide range of hydrophobic compounds, among them fatty acids 12-20 carbon atoms long. Shorter fatty acids were reported as not binding to β-lactoglobulin. We used X-ray crystallography and fluorescence spectroscopy to show that lactoglobulin binds also 8- and 10-carbon caprylic and capric acids, however with lower affinity. The determined apparent association constant for lactoglobulin complex with caprylic acid is 10.8 ± 1.7 × 10(3) M(-1), while for capric acid is 6.0 ± 0.5 × 10(3) M(-1). In crystal structures determined with resolution 1.9 Å the caprylic acid is bound in upper part of central calyx near polar residues located at CD loop, while the capric acid is buried deeper in the calyx bottom and does not interact with polar residues at CD loop. In both structures, water molecule hydrogen-bonded to carboxyl group of fatty acid is observed. Different location of ligands in the binding site indicates that competition between polar and hydrophobic interactions is an important factor determining position of the ligand in β-barrel.

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“…10 log) in a 1000‐L plasma pool, when NAT tested and the load is not higher than 10 4 /mL. Consequently, production processes of immunoglobulins and albumin must essentially include additional dedicated virus inactivation and/or removal procedures, such as pasteurization, 20 low pH treatment, 11,21 S/D treatment, 12,22‐24 caprylate treatment, 13,25,26 virus filtration, 14,15 or other procedures to further improve on the safety margins.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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Inactivation of Lipid Enveloped Viruses by Octanoic Acid Treatment of Immunoglobulin Solution

Cited by 52 publications

References 3 publications

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Two modes of fatty acid binding to bovine β‐lactoglobulin—crystallographic and spectroscopic studies

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

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