Low pH formulation of whole IgG antivenom: Impact on quality, safety, neutralizing potency and viral inactivation

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• 作者：Silvia Solano^a ; Á ; lvaro Segura^a ; Guillermo Leó ; n^a ; José ; -Marí ; a Gutié ; rrez^a ; Thierry Burnouf^b ; ^{tburnou@attglobal.net}
• 关键词：Antivenom ; Low pH ; Virus ; Inactivation
• 刊名：Biologicals
• 出版年：2012
• 期刊代码：162_10451056
• 类别：bio
• 出版时间：March, 2012
• 卷：40
• 期：2
• 页码：129-133
• 文件大小：394 K

摘要

Low pH treatment improves the tolerance to intravenous infusion, the stability, and the viral safety of various therapeutic immunoglobulins G preparations, but has never been evaluated for horse plasma-derived antivenoms. We have studied the impact of low pH formulation on the quality, safety, stability, potency and viral inactivation of a whole IgG antivenom used to treat viperid snake bite envenoming. Horse plasma-derived whole immunoglobulins purified by caprylic acid were incubated for 24聽h at low pH in the presence of 4%sorbitol, then sterile-filtered and stored liquid at 2-8聽掳C. Appearance, aggregates, purity, safety tests in mice, venom antibody titre, and neutralization potency tests were controlled. Low pH treatment did not affect the physico-chemical characteristics, safety and potency of antivenom for at least 6 months of storage, but a major increase in aggregates was observed. In聽vitro antibody titre and in聽vivo neutralizing potency were maintained. There were 鈮ヂ?.5 log inactivation of Herpes Simplex Virus-1, an enveloped virus, but no significant inactivation of the non-enveloped Poliovirus type 3. Low pH treatment appears feasible to improve the viral safety of antivenoms without affecting the neutralization potency. The possibility to formulate antivenoms at low pH requires further investigations to avoid formation of aggregates.