R. Audran et al., ENHANCED IMMUNOGENICITY OF MICROENCAPSULATED TETANUS TOXOID WITH STABILIZING AGENTS, Pharmaceutical research, 15(7), 1998, pp. 1111-1116
Purpose. Antigenic proteins encapsulated in biodegradable polyester mi
crospheres (MS) can slowly denature or aggregate, which results in dec
reased antigenicity. In this study, we have evaluated the ability of c
o-encapsulated additives to protect against the loss of tetanus toroid
(TT) antigenicity. Methods, Antibody responses were analyzed after im
munization of mice with TT microencapsulated in the presence of additi
ves (TT-MS-additive). Results. Immunization with TT-MS-additives gave
rise to higher responses than those obtained in the absence of additiv
e. BSA, trehalose, gamma-hydroxypropylcyclodextrin and calcium salts p
reserved the immunogenicity of the incorporated antigen with the highe
st efficacy. Sustained responses were obtained with mixtures of fast a
nd slowly releasing TT-MS containing BSA plus trehalose or calcium sal
ts. Conclusions. The selected additives may stabilize the antigen in M
S during storage and rehydration in body fluids. Regulated antigen rel
ease from MS-based vaccines permits a reduction of the antigen dose an
d optimization of single-dose vaccine formulations.