Champion Cheryl I, Kickhoefer Valerie A, Liu Guangchao, Moniz Raymond J, Freed Amanda S, Bergmann Liisa L, Vaccari Dana, Raval-Fernandes Sujna, Chan Ann M, Rome Leonard H, Kelly Kathleen A
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2009;4(4):e5409. doi: 10.1371/journal.pone.0005409. Epub 2009 Apr 30.
Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication.
METHODOLOGY/PRINCIPAL FINDINGS: We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants.
CONCLUSIONS/SIGNIFICANCE: Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as "smart adjuvants" for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation.
在黏膜表面产生强大的细胞介导免疫反应同时减轻整体炎症是疫苗接种的主要目标。在此，我们报告使用重组纳米颗粒作为疫苗递送平台，以对抗需要T细胞介导免疫来根除的黏膜感染。
方法/主要发现：我们将一种免疫原性蛋白——鼠衣原体的主要外膜蛋白（MOMP）包裹在中空的穹窿体纳米胶囊（MOMP-穹窿体）中，该纳米胶囊经过工程改造可结合IgG以增强免疫力。用MOMP-穹窿体进行鼻内免疫（i.n）可诱导抗衣原体免疫，并且在攻击感染后显著减轻细菌负荷。穹窿体免疫诱导了抗衣原体免疫反应和炎性小体形成，但未激活Toll样受体。此外，MOMP-穹窿体免疫增强了微生物的根除，且没有通常与佐剂相关的炎症。
结论/意义：通过鼻内途径递送至呼吸道的含有免疫原性蛋白的穹窿体纳米颗粒可作为“智能佐剂”，在远处黏膜表面诱导保护性免疫，同时避免破坏性炎症。
