Enhanced immunogenicity of microencapsulated tetanus toxoid with stabilizing agents.
OBJECTIVE
Antigenic proteins encapsulated in biodegradable polyester microspheres (MS) can slowly denature or aggregate, which results in decreased antigenicity. In this study, we have evaluated the ability of co-encapsulated additives to protect against the loss of tetanus toxoid (TT) antigenicity.


METHODS
Antibody responses were analyzed after immunization of mice with TT microencapsulated in the presence of additives (TT-MS-additive).


RESULTS
Immunization with TT-MS-additives gave rise to higher responses than those obtained in the absence of additive. BSA, trehalose. Gamma-hydroxypropylcyclodextrin and calcium salts preserved the immunogenicity of the incorporated antigen with the highest efficacy. Sustained responses were obtained with mixtures of fast and slowly releasing TT-MS containing BSA plus trehalose or calcium salts.


CONCLUSIONS
The selected additives may stabilize the antigen in MS during storage and rehydration in body fluids. Regulated antigen release from MS-based vaccines permits a reduction of the antigen dose and optimization of single-dose vaccine formulations.
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
R
R
Audran
Y
Y
Men
P
P
Johansen
B
B
Gander
G
G
Corradin
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*
D000907:Antibodies, Bacterial; D002214:Capsules; D005079:Excipients; D011108:Polymers; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid