Liquid pasteurization of an immunoglobulin preparation without stabilizer: effects on its biological and biochemical properties.
Intravenous immunoglobulins (IVIg) purified by cold ethanol fractionation have a very good safety record with regard to the transmission of many viruses. However, a few cases of non-A-non-B hepatitis have been described after intravenous injection of some immunoglobulin preparations. To ensure even higher safety for our IVIg, an additional virus inactivation step, based on pasteurization, was developed. The heating of aqueous IVIg was performed without stabilizer, and at a very low salt concentration (< 1 mM) at acidic pH. No generation of polymer was detected after pasteurization and a significant decrease in the proportion of dimers was observed. Analysis of the secondary structure by circular dichroism showed a very slight change in the secondary structure. The biological properties of the Fc region as well as the Fab region were not affected by the pasteurization. Our method has several advantages: (1) improvement of viral safety; (2) there is no need to add stabilizer which may stabilize viral particles, and (3) the absence of any hypotensive effect and low anticomplementary activity indicates a good clinical tolerance of IgG preparation.
Bridonneau
P
P
Fondation Nationale de la Transfusion Sanguine, Recherche et Développement, Les Ulis, France.
Marcilly
H
H
Vernois-Martin
M
M
Goigoux
P
P
Bourdel
V
V
Laulan
A
A
Deramoudt
F X
FX
Desmadril
M
M
Sitbon
M
M
Basuyaux
B
B
Steinbuch
M
M
Schmitthaeusler
R
R
D000818:Animals; D010584:Bacteriophage phi X 174 / Q000302:isolation & purification / Q000502:physiology; D001769:Blood / Q000276:immunology / Q000821:virology; D002942:Circular Dichroism; D003080:Cold Temperature; D003956:Dialysis; D019281:Dimerization; D000431:Ethanol; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007022:Hypotension / Q000139:chemically induced; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D051381:Rats; D012449:Safety; D013242:Sterilization / Q000379:methods*; D014779:Virus Replication
D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D000431:Ethanol