Stabilization of alum-adjuvanted vaccine dry powder formulations: Mechanism and application

Stabilization of alum-adjuvanted vaccine dry powder formulations: Mechanism and application
February 1, 2003
YF Maa, L Zhao, LG Payne, and D Chen
Journal of Pharmaceutical Sciences
HighWire Press
PowderJect Vaccines, Inc. 585 Science Drive, Madison, Wisconsin 53711, USA. yuh-fun.maa@alza.com
Download to Citation Manager
Alert me when this article is cited
PubMed Citation
Related Articles in PubMed
Order Full text via Infotrieve
Publisher's Full Text Link

Studies were performed to elucidate the mechanism of alum gel coagulation upon freezing and drying and its relationship to vaccine potency loss and to develop a novel freeze-drying process for the production of stable alum-adjuvanted vaccine formulations suitable for conventional needle injection and epidermal powder immunization (EPI). The alum hydroxide-adjuvanted hepatitis-B surface antigen (Alum-HBsAg) and the alum phosphate-adjuvanted diphtheria and tetanus toxoids (Alum-DT) were dehydrated by freeze drying (FD), spray drying (SD), air drying (AD), or spray freeze drying (SFD). After drying by FD, SD, or AD, alum gels coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated when examined by optical microscopy and particle size analysis. In addition, desorption of antigen molecules from the coagulated alum gel upon reconstitution appeared to be difficult, as indicated by attenuated band intensity on SDS-PAGE. In contrast, SFD alum gels turned a homogenous suspension upon reconstitution, suggesting minimal alum coagulation. In the mouse model, the in vivo immunogenicity of SFD Alum-HBsAg was preserved, whereas the FD Alum-HBsAg suffered significant immunogenicity loss. Grinding of coagulated FD Alum-HBsAg into smaller particles could partially recover the immunogenicity. In a guinea pig study using EPI, the SD Alum-DT formulation was not immunogenic, but the SFD Alum-DT formulations had a vaccine potency comparable to that of the untreated DT administered by I.M. injection. Overall, the relationship of coagulation of alum gel upon reconstitution and the loss of vaccine potency was established in this study. Alum gels became highly coagulated after dehydration by spray drying and traditional freeze-drying processes. However, freezing rate played a critical role in preserving the adjuvant effect of alum and fast freezing decreased the tendency of alum coagulation. Spraying the alum gel into liquid nitrogen represents the fastest freezing rate achievable and resulted in no discernible alum coagulation. Therefore, SFD presents a novel and effective drying process for alum-adjuvanted vaccine formulations and is particularly valuable for dry powder applications such as EPI.
Publication Type:
Journal article
MeSH Terms:
Adjuvants, Immunologic
Alum Compounds
Animals
Antibody Formation
Chemistry, Pharmaceutical
Diphtheria Toxoid
Drug Compounding
Drug Stability
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Female
Freeze Drying
Guinea Pigs
Hepatitis B Vaccines
Mice
Mice, Inbred BALB C
Particle Size
Powders
Vaccines
PMID: 12532382

This is a subscription site. You will need to register and pay to view the Full Text Article.