Department of Veterinary Pathology, Iowa State University, Ames, IA 50011, USA.
Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA.
Vaccine. 2018 Feb 8;36(7):1016-1023. doi: 10.1016/j.vaccine.2017.12.050.
Traditionally, vaccination strategies require an initial priming vaccination followed by an antigen boost to generate adequate immunity. Here we describe vaccination against a self-peptide for reproductive sterilization utilizing a three-stage vaccine platform consisting of gonadotropin releasing hormone multiple antigenic peptide (GnRH-MAP) as a soluble injection coupled with subcutaneous administration of polyanhydride-immobilized GnRH-MAP and a cyto-exclusive implant containing GnRH-MAP dendrimer-loaded polyanhydride. This strategy generated and maintained cell-mediated and humoral immunity for up to 41 weeks after a single vaccination in mice with enhanced antibody avidity over time. All intact implants had a grossly visible tissue interface with neovascularization and lymphocytic aggregates. Despite detectable immunity, sterility was not achieved and the immune response did not lead to azoospermia in male mice nor prevent estrus and ovulation in female mice. However, the vaccine delivery device is tunable and the immunogen, adjuvants and release rates can all be modified to enhance immunity. This technology has broad implications for the development of long-term vaccination schemes.
传统上，疫苗接种策略需要初始的基础免疫接种，然后进行抗原增强，以产生足够的免疫力。在这里，我们描述了一种利用三阶段疫苗平台针对生殖绝育的自身肽疫苗接种，该平台由促性腺激素释放激素多抗原肽（GnRH-MAP）作为可溶性注射剂与皮下给予聚酸酐固定 GnRH-MAP 和含有 GnRH-MAP 树突状聚合物负载聚酸酐的细胞外排斥植入物联合使用。这种策略在小鼠中产生并维持了细胞介导和体液免疫，在单次接种后长达 41 周，并且随着时间的推移抗体亲和力增强。所有完整的植入物都有一个明显可见的组织界面，伴有新生血管和淋巴细胞聚集。尽管存在可检测的免疫，但并未达到不育效果，并且免疫反应并未导致雄性小鼠无精子症，也未阻止雌性小鼠发情和排卵。然而，疫苗输送装置是可调节的，免疫原、佐剂和释放率都可以进行修改以增强免疫。这项技术对于开发长期疫苗接种方案具有广泛的意义。
