New GMP manufacturing processes to obtain thermostable HIV-1 gp41 virosomes under solid forms for various mucosal vaccination routes
New GMP manufacturing processes to obtain thermostable HIV-1 gp41 virosomes under solid forms for various mucosal vaccination routes
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DOI：
10.1038/s41541-020-0190-9
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发表时间：
2020-05-18
期刊：
影响因子：
9.2
通讯作者：
Fleury, Sylvain
中科院分区：
文献类型：
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作者：
Amacker, Mario;Smardon, Charli;Fleury, Sylvain
MACIVIVA欧洲联盟的主要目标是开发新的药品生产质量管理规范中试生产线，用于生产在流感病毒体上具有稳定抗原（作为包膜病毒样颗粒）的热稳定疫苗。锚定在病毒体膜中的HIV-1 gp 41衍生抗原，与佐剂3 M-052（TLR 7/8激动剂）一起沿着在相同颗粒上，作为候选疫苗用于建立生产工艺的概念验证，其可以直接应用或适用于其他病毒体疫苗或基于脂质的颗粒。热喷雾干燥的粉末，适用于鼻腔或口腔传递，和冻干舌下片剂被成功地开发为固体剂型的粘膜接种。具有关键gp 41表位的疫苗抗原的抗原特性得以保持，保留了起始液体形式的原始免疫原性，并且当固体形式暴露于高温（40 ° C）长达3个月时，具有最小的抗原和佐剂含量变化。从粉末形式重构的病毒体保持为具有相似大小的游离颗粒，体外抗原呈递细胞对病毒体的摄取与来自液体形式的病毒体相当，并且对每种固体形式具有特异性的赋形剂的存在不会阻止病毒体转运至免疫小鼠的引流淋巴结。病毒体完整性在暴露于
The main objective of the MACIVIVA European consortium was to develop new Good Manufacturing Practice pilot lines for manufacturing thermostable vaccines with stabilized antigens on influenza virosomes as enveloped virus-like particles. The HIV-1 gp41-derived antigens anchored in the virosome membrane, along with the adjuvant 3M-052 (TLR7/8 agonist) on the same particle, served as a candidate vaccine for the proof of concept for establishing manufacturing processes, which can be directly applied or adapted to other virosomal vaccines or lipid-based particles. Heat spray-dried powders suitable for nasal or oral delivery, and freeze-dried sublingual tablets were successfully developed as solid dosage forms for mucosal vaccination. The antigenic properties of vaccinal antigens with key gp41 epitopes were maintained, preserving the original immunogenicity of the starting liquid form, and also when solid forms were exposed to high temperature (40 degrees C) for up to 3 months, with minimal antigen and adjuvant content variation. Virosomes reconstituted from the powder forms remained as free particles with similar size, virosome uptake by antigen-presenting cells in vitro was comparable to virosomes from the liquid form, and the presence of excipients specific to each solid form did not prevent virosome transport to the draining lymph nodes of immunized mice. Virosome integrity was also preserved during exposure to