Choi In-Jeong, Cha Hye-Ran, Hwang Su Jin, Baek Seung-Ki, Lee Jae Myun, Choi Seong-O
QuadMedicine R&D Centre, QuadMedicine, Inc., Seongnam 13209, Korea.
Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea.
Pharmaceutics. 2021 Feb 3;13(2):209. doi: 10.3390/pharmaceutics13020209.
Although smallpox has been eradicated globally, the potential use of the smallpox virus in bioterrorism indicates the importance of stockpiling smallpox vaccines. Considering the advantages of microneedle-based vaccination over conventional needle injections, in this study, we examined the feasibility of microneedle-based smallpox vaccination as an alternative approach for stockpiling smallpox vaccines. We prepared polylactic acid (PLA) microneedle array patches by micromolding and loaded a second-generation smallpox vaccine on the microneedle tips via dip coating. We evaluated the effect of excipients and drying conditions on vaccine stability in vitro and examined immune responses in female BALB/c mice by measuring neutralizing antibodies and interferon (IFN)-γ-secreting cells. Approximately 40% of the virus titer was reduced during the vaccine-coating process, with or without excipients. At -20 °C, the smallpox vaccine coated on the microneedles was stable up to 6 months. Compared to natural evaporation, vacuum drying was more efficient in improving the smallpox vaccine stability. Microneedle-based vaccination of the mice elicited neutralizing antibodies beginning 3 weeks after immunization; the levels were maintained for 12 weeks. It significantly increased IFN-γ-secreting cells 12 weeks after priming, indicating the induction of cellular immune responses. The smallpox-vaccine-coated microneedles could serve as an alternative delivery system for vaccination and stockpiling.
虽然天花已在全球范围内被根除，但天花病毒在生物恐怖主义中的潜在用途表明储备天花疫苗的重要性。考虑到基于微针的疫苗接种相对于传统针头注射的优势，在本研究中，我们研究了基于微针的天花疫苗接种作为储备天花疫苗的替代方法的可行性。我们通过微模塑制备了聚乳酸（PLA）微针阵列贴片，并通过浸涂将第二代天花疫苗加载到微针尖端。我们评估了辅料和干燥条件对疫苗体外稳定性的影响，并通过测量中和抗体和干扰素（IFN）-γ分泌细胞来检测雌性BALB/c小鼠的免疫反应。在疫苗包被过程中，无论有无辅料，病毒滴度大约降低40%。在-20℃下，包被在微针上的天花疫苗在长达6个月的时间内保持稳定。与自然蒸发相比，真空干燥在提高天花疫苗稳定性方面更有效。基于微针的小鼠疫苗接种在免疫后3周开始产生中和抗体；抗体水平维持了12周。初次免疫12周后，它显著增加了IFN-γ分泌细胞，表明诱导了细胞免疫反应。包被有天花疫苗的微针可作为疫苗接种和储备的替代递送系统。
