Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
Vaccine. 2018 May 31;36(23):3331-3339. doi: 10.1016/j.vaccine.2018.04.055. Epub 2018 Apr 24.
Liquid vaccine dosage forms have limited stability and require refrigeration during their manufacture, distribution and storage. In contrast, solid vaccine dosage forms, produced by for example spray drying, offer improved storage stability and reduced dependence on cold-chain facilities. This is advantageous for mass immunization campaigns for global public health threats, e.g., tuberculosis (TB), and offers cheaper vaccine distribution. The multistage subunit vaccine antigen H56, which is a fusion protein of the Mycobacterium tuberculosis (Mtb) antigens Ag85B, ESAT-6, and Rv2660, has been shown to confer protective efficacy against active TB before and after Mtb exposure in preclinical models, and it is currently undergoing clinical phase 2a testing. In several studies, including a recent study comparing multiple clinically relevant vaccine adjuvants, the T helper type 1 (Th1)/Th17-inducing adjuvant CAF01 was the most efficacious adjuvant for H56 to stimulate protective immunity against Mtb. With the long-term goal of designing a thermostable and self-administrable dry powder vaccine based on H56 and CAF01 for inhalation, we compared H56 spray-dried with CAF01 with the non-spray-dried H56/CAF01 vaccine with respect to their ability to induce systemic Th1, Th17 and humoral responses after subcutaneous immunization. Here we show that spray drying of the H56/CAF01 vaccine results in preserved antigenic epitope recognition and adjuvant activity of CAF01, and the spray-dried, reconstituted vaccine induces antigen-specific Th1, Th17 and humoral immune responses, which are comparable to those stimulated by the non-spray-dried H56/CAF01 vaccine. In addition, the spray-dried and reconstituted H56/CAF01 vaccine promotes similar polyfunctional CD4 T-cell responses as the non-spray-dried vaccine. Thus, our study provides proof-of-concept that spray drying of the subunit vaccine H56/CAF01 preserves vaccine-induced humoral and cell-mediated immune responses. These results support our ongoing efforts to develop a thermostable, dry powder-based TB vaccine.
液体疫苗剂型在制造、分发和储存过程中稳定性有限，需要冷藏。相比之下，通过喷雾干燥等方法生产的固体疫苗剂型具有更好的储存稳定性，对冷链设施的依赖性降低。这对于针对全球公共卫生威胁（如结核病，TB）的大规模免疫接种运动非常有利，并且降低了疫苗分发成本。多阶段亚单位疫苗抗原 H56 是结核分枝杆菌（Mtb）抗原 Ag85B、ESAT-6 和 Rv2660 的融合蛋白，已在临床前模型中证明在 Mtb 暴露前后对活性 TB 具有保护效力，目前正在进行临床 2a 期试验。在几项研究中，包括最近一项比较多种临床相关疫苗佐剂的研究，辅助 H56 刺激针对 Mtb 的保护性免疫的 Th1/Th17 诱导佐剂 CAF01 是最有效的佐剂。我们的长期目标是设计一种基于 H56 和 CAF01 的耐热、可自我给药的干粉疫苗，用于吸入，我们比较了喷雾干燥的 H56/CAF01 与非喷雾干燥的 H56/CAF01 疫苗在皮下免疫后诱导全身 Th1、Th17 和体液反应的能力。在这里，我们表明 H56/CAF01 疫苗的喷雾干燥导致保留抗原表位识别和 CAF01 的佐剂活性，并且喷雾干燥、重构的疫苗诱导抗原特异性 Th1、Th17 和体液免疫反应，与非喷雾干燥的 H56/CAF01 疫苗刺激的反应相当。此外，喷雾干燥和重构的 H56/CAF01 疫苗促进与非喷雾干燥疫苗相似的多功能 CD4 T 细胞反应。因此，我们的研究提供了概念验证，即 H56/CAF01 亚单位疫苗的喷雾干燥保留了疫苗诱导的体液和细胞介导的免疫反应。这些结果支持我们正在进行的努力，开发一种耐热、基于干粉的 TB 疫苗。
