Weissmueller Nikolas T, Marsay Leanne, Schiffter Heiko A, Carlisle Robert C, Rollier Christine S, Prud'homme Robert K, Pollard Andrew J
Department of Paediatrics, Oxford Vaccine Group, University of Oxford and the NIHR Oxford Biomedical Research Institute, Oxford, Oxfordshire, United Kingdom.
Department of Biological and Chemical Engineering, Princeton University, Princeton, New Jersey, United States of America.
PLoS One. 2017 Aug 24;12(8):e0183427. doi: 10.1371/journal.pone.0183427. eCollection 2017.
Powder-injectors use gas propulsion to deposit lyophilised drug or vaccine particles in the epidermal and sub epidermal layers of the skin. We prepared dry-powder (Tg = 45.2 ± 0.5°C) microparticles (58.1 μm) of a MenY-CRM197 glyconjugate vaccine (0.5% wt.) for intradermal needle-free powder injection (NFPI). SFD used ultrasound atomisation of the liquid vaccine-containing excipient feed, followed by lyophilisation above the glass transition temperature (Tg' = - 29.9 ± 0.3°C). This resulted in robust particles (density~ 0.53 ±0.09 g/cm3) with a narrow volume size distribution (mean diameter 58.1 μm, and span = 1.2), and an impact parameter (ρvr ~ 11.5 kg/m·s) sufficient to breach the Stratum corneum (sc). The trehalose, manitol, dextran (10 kDa), dextran (150 kDa) formulation, or TMDD (3:3:3:1), protected the MenY-CRM197 glyconjugate during SFD with minimal loss, no detectable chemical degradation or physical aggregation. In a capsular group Y Neisseria meningitidis serum bactericidal assay (SBA) with human serum complement, the needle free vaccine, which contained no alum adjuvant, induced functional protective antibody responses in vivo of similar magnitude to the conventional vaccine injected by hypodermic needle and syringe and containing alum adjuvant. These results demonstrate that needle-free vaccination is both technically and immunologically valid, and could be considered for vaccines in development.
粉末注射器利用气体推进将冻干的药物或疫苗颗粒沉积在皮肤的表皮和皮下层。我们制备了用于皮内无针粉末注射（NFPI）的MenY-CRM197糖缀合物疫苗（0.5%重量）的干粉（玻璃化转变温度Tg = 45.2±0.5°C）微粒（58.1μm）。喷雾冷冻干燥法（SFD）使用含疫苗的液体辅料进料进行超声雾化，然后在高于玻璃化转变温度（Tg' = - 29.9±0.3°C）下进行冻干。这产生了坚固的颗粒（密度约为0.53±0.09 g/cm³），其体积尺寸分布狭窄（平均直径58.1μm，跨度 = 1.2），并且冲击参数（ρvr约为11.5 kg/m·s）足以穿透角质层（sc）。海藻糖、甘露醇、右旋糖酐（10 kDa）、右旋糖酐（150 kDa）配方，即TMDD（3:3:3:1），在喷雾冷冻干燥过程中保护了MenY-CRM197糖缀合物，损失最小，没有可检测到的化学降解或物理聚集。在用人血清补体进行的Y群脑膜炎奈瑟菌血清杀菌试验（SBA）中，不含明矾佐剂的无针疫苗在体内诱导的功能性保护性抗体反应的幅度与皮下注射含明矾佐剂的传统疫苗相似。这些结果表明，无针接种在技术和免疫学上都是有效的，可考虑用于正在研发的疫苗。
