Enhancing the immune response to vaccines and minimizing the need for repeated inoculations remain a challenge in clinical vaccination. This study developed a composite microneedle (MN), composed of a sodium hyaluronate (HA) tip and a chitosan base, for biphasic antigen release and evaluated the potential of using this MN formulation as an intradermal delivery system for single-dose vaccination. Upon skin insertion, the dissolvable HA tip dissolved within the skin for rapid release of the encapsulated antigens, thus priming the immune system, while the biodegradable chitosan base remained in the dermis for prolonged antigen release for 4 weeks, thus further boosting the stimulated immunity. Our results showed that a single immunization with the HA/chitosan MN containing ovalbumin (OVA) (100 μg × 1) stimulated both T helper type 1 (Th1) and Th2 immune responses in rats and induced considerably higher and more durable antibody responses than a traditional two-dose (100 μg OVA × 2) or double-dose (200 μg OVA × 1) subcutaneous vaccination. Thus, the proposed MN exerts strong adjuvanticity to greatly augment the antigen’s immunogenicity. Moreover, given its unique rapid and sustained release properties, the HA/chitosan MN formulation has the potential to replace the conventional prime–boost regimen to serve as an effective single-dose vaccine formulation.

中文翻译：

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透明质酸钠/壳聚糖复合微针作为单剂量皮内免疫系统

增强对疫苗的免疫反应并使对重复接种的需求最小化仍然是临床疫苗接种中的挑战。这项研究开发了一种由玻尿酸钠（HA）尖端和壳聚糖碱组成的复合微针（MN），用于双相抗原释放，并评估了将该MN制剂用作单剂量疫苗接种的皮内递送系统的潜力。插入皮肤后，可溶解的HA尖端溶解在皮肤中，以快速释放被包封的抗原，从而引发免疫系统，而可生物降解的壳聚糖碱则保留在真皮中，以延长抗原释放4周，从而进一步增强了刺激的免疫力。我们的研究结果表明，用含卵清蛋白（OVA）（100μg×1）的HA /壳聚糖MN进行的单次免疫刺激可刺激大鼠T辅助1型（Th1）和Th2免疫反应，并诱导出比A辅助人更高，更持久的抗体反应。传统的两剂（100μgOVA×2）或双剂（200μgOVA×1）皮下接种。因此，拟议的MN具有强大的佐剂性，可以大大增强抗原的免疫原性。此外，鉴于其独特的快速和持续释放特性，HA /壳聚糖MN制剂有可能取代传统的初免-加强疗法，成为有效的单剂量疫苗制剂。