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Enhanced Immunogenicity of Microencapsulated Tetanus Toxoid with Stabilizing Agents

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Abstract

Purpose. 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, -γ-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.

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Authors and Affiliations

  1. Institute of Biochemistry, University of Lausanne, CH-1066, Epalinges, Switzerland

    Régine Audran, Ying Men & Giampietro Corradin

  2. Departement of Pharmacy, ETH, 8058, Zurich, Switzerland

    Pål Johansen & Bruno Gander

Authors
  1. Régine Audran
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  2. Ying Men
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  3. Pål Johansen
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  4. Bruno Gander
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  5. Giampietro Corradin
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Audran, R., Men, Y., Johansen, P. et al. Enhanced Immunogenicity of Microencapsulated Tetanus Toxoid with Stabilizing Agents. Pharm Res 15, 1111–1116 (1998). https://doi.org/10.1023/A:1011950732105

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