Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands; University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
J Control Release. 2018 Sep 28;286:167-178. doi: 10.1016/j.jconrel.2018.07.035. Epub 2018 Jul 24.
Worldwide resurgence of whooping cough calls for improved, next-generation pertussis vaccines that induce broad and long-lasting immunity. A mucosal pertussis vaccine based on outer membrane vesicles (omvPV) is a promising candidate. Further, a vaccine that is stable outside the cold chain would be of substantial advantage for worldwide distribution and application. A vaccine formulated as a powder could both stabilize the vaccine as well as make it suitable for pulmonary vaccination. To that end, we developed a spray dried omvPV with improved stability compared to the liquid omvPV formulation. Spray drying did not affect the structural integrity of the omvPV. The antigenicity of Vag8, a major antigen in omvPV was diminished slightly and an altered tryptophan fluorescence indicated some changes in protein structure. However, when administered via the pulmonary route in mice after reconstitution, spray dried omvPV showed comparable immune responses and protection against challenge with live B. pertussis as liquid omvPV. Mucosal IgA and Th17 responses were established in addition to broad systemic IgG and Th1/Th17 responses, indicating the induction of an effective immunity profile. Overall, a spray dried omvPV was developed that maintained effective immunogenic properties and has an improved storage stability.
全球百日咳卷土重来，需要改进下一代百日咳疫苗，以诱导广泛和持久的免疫力。基于外膜囊泡 (omvPV) 的粘膜百日咳疫苗是一种很有前途的候选疫苗。此外，对于全球分发和应用而言，一种在冷链之外稳定的疫苗将具有实质性的优势。制成粉末的疫苗既可以稳定疫苗，又可以使其适合肺部接种。为此，我们开发了一种喷雾干燥的 omvPV，与液体 omvPV 制剂相比，其稳定性得到了改善。喷雾干燥不会影响 omvPV 的结构完整性。 Vag8 是 omvPV 中的主要抗原，其抗原性略有降低，色氨酸荧光的改变表明蛋白质结构发生了一些变化。然而，当以干粉形式经肺部途径在小鼠中重新配制后，喷雾干燥的 omvPV 显示出与液体 omvPV 相当的免疫反应和对活 B. pertussis 挑战的保护作用。除了广泛的系统 IgG 和 Th1/Th17 反应外，还建立了粘膜 IgA 和 Th17 反应，表明诱导了有效的免疫状态。总的来说，开发了一种喷雾干燥的 omvPV，它保持了有效的免疫原性，并具有改善的储存稳定性。
