Yim Sang-Gu, Hwang Yun-Ho, An Seonyeong, Seong Keum-Yong, Kim Seo-Yeon, Kim Semin, Lee Hyeseon, Lee Kang-Oh, Kim Mi-Young, Kim Dokeun, Kim You-Jin, Yang Seung-Yun
Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Korea.
Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Korea.
Vaccines (Basel). 2022 Apr 4;10(4):561. doi: 10.3390/vaccines10040561.
Smallpox is an acute contagious disease caused by the variola virus. According to WHO guidelines, the smallpox vaccine is administrated by scarification into the epidermis using a bifurcated needle moistened with a vaccine solution. However, this invasive vaccination method involving multiple skin punctures requires a special technique to inoculate, as well as a cold chain for storage and distribution of vaccine solutions containing a live virus. Here, we report a transcutaneous smallpox vaccination using a live vaccinia-coated microneedle (MN) patch prepared by a low-temperature multiple nanoliter-level dispensing system, enabling accurate transdermal delivery of live vaccines and maintenance of bioactivity. The live vaccinia in hyaluronic acid (HA) solutions was selectively coated on the solid MN tips, and the coating amount of the vaccine was precisely controlled through a programmed multiple dispensing process with high accuracy under low temperature conditions (2-8 °C) for smallpox vaccination. Inoculation of mice (BALB/C mouse) with the MN patch coated with the second-generation smallpox vaccine increased the neutralizing antibody titer and T cell immune response. Interestingly, the live vaccine-coated MN patch maintained viral titers at -20 °C for 4 weeks and elevated temperature (37 °C) for 1 week, highlighting improved storage stability of the live virus formulated into coated MN patches. This coated MN platform using contact dispensing technique provides a simple and effective method for smallpox vaccination.
天花是一种由天花病毒引起的急性传染病。根据世界卫生组织的指导方针，天花疫苗通过使用蘸有疫苗溶液的分叉针划破表皮来接种。然而，这种涉及多次皮肤穿刺的侵入性接种方法需要特殊的接种技术，以及用于储存和分发含有活病毒的疫苗溶液的冷链。在此，我们报告了一种使用由低温多纳升水平分配系统制备的活牛痘包被微针（MN）贴片进行经皮天花接种的方法，该方法能够实现活疫苗的精确透皮递送并维持生物活性。将透明质酸（HA）溶液中的活牛痘选择性地包被在固体MN尖端，并通过在低温条件（2-8°C）下进行的高精度程序化多次分配过程精确控制疫苗的包被量，用于天花接种。用包被有第二代天花疫苗的MN贴片接种小鼠（BALB/C小鼠）可提高中和抗体滴度和T细胞免疫反应。有趣的是，包被有活疫苗的MN贴片在-20°C下可保持病毒滴度4周，在高温（37°C）下可保持1周，这突出了配制在包被MN贴片中的活病毒储存稳定性的提高。这种使用接触式分配技术的包被MN平台为天花接种提供了一种简单有效的方法。
