Rational design of an influenza subunit vaccine powder with sugar glass technology: Preventing conformational changes of haemagglutinin during freezing and freeze-drying

被引：88

作者：

Amorij, J.-P.

Meulenaar, J.

Hinrichs, W. L. J.

Stegmann, T.

Huckriede, A.

Coenen, F.

Frijlink, H. W.

机构：

[1] Univ Groningen, Dept Pharmaceut Technol & Biopharm, NL-9713 AV Groningen, Netherlands

[2] Virosome Biol, NL-2333 AL Leiden, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Mol Virol Sect, Dept Med Microbiol, NL-9713 AV Groningen, Netherlands

[4] Solvay Pharmaceut, NL-1381 CP Weesp, Netherlands

来源：

VACCINE | 2007年 / 25卷 / 35期

关键词：

influenza vaccine; buffer; lyophilization;

D O I：

10.1016/j.vaccine.2007.06.054

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The development of a stable influenza subunit vaccine in the dry state was investigated. The influence of various carbohydrates, buffer types and freezing rates on the integrity of haemagglutinin after freeze-thawing or freeze-drying was investigated with a range of analytical and immunological methods. The use of fast freezing, Hepes buffer and carbohydrates (trehalose, inulin or dextran) as cryo- and lyoprotectants resulted in a significant reduction or even absence of conformational changes of HA as revealed by the used methods. The subunit vaccine in the powder was shown to remain immunogenic in an in vivo study in mice, using reconstituted powder. Moreover, the HA potency of the influenza subunit vaccine powder was stable for at least 26 weeks at room temperature. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：6447 / 6457

页数：11

共 42 条

[11] The relationship between protein aggregation and molecular mobility below the glass transition temperature of lyophilized formulations containing a monoclonal antibody [J].