单剂量破伤风类毒素微球在动物体内的药效

Immunogenicity of single-dose delivery of tetanus toxoid encapsulated in microspheres

目的 :研究经破伤风类毒素聚乳酸微球免疫后的动物体内药效。方法 :测定破伤风类毒素聚乳酸微球免疫动物后 1年中动物血清抗体反应及疫苗制剂的生物利用度。结果 :单剂量聚乳酸微球制剂引起高水平的血清抗体效价 ,具有与疫苗常规的 3次免疫相似的药效。混合微球制剂的相对生物利用度为 1 0 7.0 9%。 1年后 3剂破伤风类毒素溶液引起的免疫记忆抗体效价为 5 .2× 1 0 6 ,而混合微球引起的免疫记忆抗体效价为 2 .6× 1 0 7。结论 :创制了单剂量疫苗制剂 ,一次注射完成全程免疫 。

Objective: To evaluate immunogenicity of tetanus toxoid(TT) encapsulated in polymer microspheres composed of polylactide(PLA). Methods: The antibody levels elicited by microsphere formulations in mice for 1 year were examined, and the bioavailability of microsphere formulations was calculated. Results: Single dose microsphere formulations elicited significantly high IgG antibody levels. The immunogenicity elicited by microsphere formulations was similar to that elicited by the routine immunization with three doses of vaccine solution. The bioavailability of microsphere mixtures was 107.09%. Potency of anamnestic antibody responses of mice primed with three doses of vaccine solution was 5.2×10 6, while with microsphere mixtures 2.6×10 7. Conclusion: We have developed a drug delivery system to accomplish the conversion of multiple dose vaccines into single dose, which may represent an important advance leading to improved vaccine and vaccination.