Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy

Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen‐presenting cells (APCs; e.g., dendritic cells) or T cells are educated using immunomodulatory agents including tumor‐associated antigens and adjuvants, and manipulated to induce a cascading adaptive immune response targeting tumor cells. Mesoporous silica materials are promising candidates to improve cancer immunotherapy based on their attractive properties that include high porosity, high biocompatibility, facile surface modification, and self‐adjuvanticity. Here, the recent progress on mesoporous‐silica‐based immunotherapies based on two material forms is summarized: 1) mesoporous silica nanoparticles (MSNs), which can be internalized into APCs, and 2) micrometer‐sized mesoporous silica rods (MSRs) that can form a 3D space to recruit APCs. Subcutaneously injected MSN‐based cancer vaccines can be taken up by peripheral APCs or by APCs in lymphoid organs to educate the immune system against cancer cells. MSR cancer vaccines can recruit immune cells into the MSR scaffold to induce cancer‐specific immunity. Both vaccine systems successfully stimulate the adaptive immune response to eradicate cancer in vivo. Thus, mesoporous silica has potential value as a material platform for the treatment of cancer or infectious diseases.     

适用于疫苗低温保存冷库的空气压缩制冷系统性能研究

基于空气制冷系统制冷剂安全环保且可就地取材、蒸发器无需除霜的特点,本文研究了其应用于-70 ℃低温疫苗冷库的性能和可行性,与文献对比验证了热力学模型的准确性,并与复叠式制冷系统进行了性能对比。结果表明：在环境温度35 ℃时,采用三级压缩（总压比为8）和回热器（夹点温差为5 ℃）的空气制冷系统的COP在库温-70~10 ℃范围内为0.23~0.38,基本呈线性变化,在-70 ℃时比复叠式制冷系统COP小25.8%;在环境温度升高10 ℃时空气制冷系统COP和制冷量仅降低5%和3%,变化程度远小于复叠式制冷循环（COP降低15%,制冷量降低8%）,因此环境温度对库温造成的波动更小;空气制冷系统可以通过调节出气状态来改变送风压差,对疫苗冷库进行均匀送风。相比复叠式制冷系统减少了风机设备成本功耗,调节更加方便。因此,空气制冷系统在-70 ℃以下温区应用于疫苗低温保存具有很高的可靠性和稳定性,特别适用于疫苗低温运输设备,具有很大应用潜力。     

Biomimetic Nanomaterial Strategies for Virus Targeting: Antiviral Therapies and Vaccines

The ongoing coronavirus disease 2019 (COVID-19) pandemic highlights the importance of developing effective virus targeting strategies to treat and prevent viral infections. Since virus particles are nanoscale entities, nanomaterial design strategies are ideally suited to create advanced materials that can interact with and mimic virus particles. In this progress report, the latest advances in biomimetic nanomaterials are critically discussed for combating viral infections, including in the areas of nanomaterial-enhanced viral replication inhibitors, biomimetic virus particle capture schemes, and nanoparticle vaccines. Particular focus is placed on nanomaterial design concepts and material innovations that can be readily developed to thwart future viral threats. Pertinent nanomaterial examples from the COVID-19 situation are also covered along with discussion of human clinical trial efforts underway that might lead to next-generation antiviral therapies and vaccines.     

百白破混合制剂接种反应及血清学效果

我们对新配方吸附及不吸附的百白破混合制剂进行了人群使用反应及效果观察。结果表明,免疫效果前者优于后者,免疫反应前者较明显低于后者,这为修订规程,统一配方及提高制品质量提供了依据。观察中吸附制品的无菌化脓率为0.29%。     

口服脊髓灰质炎减毒活疫苗猴体神经毒力试验病理检定分析

作者总结和分析了本所27年中(1961～1987)有关口服脊髓灰质炎减毒活疫苗(OPV)病理检定情况。按WHO检定规程要求,用脑内法检定458批,合格率85.4％,其中I型76.58％,Ⅱ型90.91％,Ⅲ型92.36％。通过脑内注射6053只猴的中枢神经系统组织学观察发现仅有少数猴(3.68％)出现无麻痹性脊髓灰质炎,亦可见到极少数猴(0.84％)出现麻痹性脊灰炎,并认为脑内试验猴应以脊髓特异性改变为病理诊断依据。用脊髓内法检定51批疫苗,全部合格。作者认为,用被检疫苗和参考制品的平均病变分值之差与基本数据比较所得的结果去评价疫苗的减毒程度是合理的。     

层析技术纯化核酸疫苗

目的利用层析技术制备高纯度的核酸疫苗。方法用层析技术中的凝胶过滤、亲和、离子交换层析3种方法,依次对核酸疫苗进行纯化,并检测其纯度。结果连续使用3种层析方法获得的DNA达到了理想的分离效果,琼脂糖凝胶电泳未检出RNA,A260与A280的比值介于1.80~2.00之间,其中环状DNA达90%以上。经离子交换层析后的内毒素含量小于10EU/mg DNA,宿主DNA残留量小于0.002μg/μg DNA。结论纯化的核酸疫苗均符合国家标准,为制备核酸疫苗奠定了基础。     

冻干水痘减毒活疫苗免疫持久性观察

目的观察国产冻干水痘减毒活疫苗的免疫原性和免疫持久性。方法选免疫前抗体阴性的健康易感儿童,随机分为3组,分别接种原倍疫苗、稀释疫苗及对照疫苗,并于接种后每年采集静脉血,用FAMA法测定抗体。结果原倍疫苗组和稀释疫苗组免疫后1~5年,平均抗体阳性率分别为91·05%、89·39%、95·56%、97·27%和98·76%。免疫后1年与5年抗体阳性率及抗体GMT比较,差异均无显著意义。原倍疫苗组和稀释疫苗组抗体阳性率及抗体GMT比较,差异亦无显著意义。接种原倍和稀释疫苗的两组与对照组比较,差异无显著意义。结论国产冻干水痘减毒活疫苗具有良好的免疫原性及免疫持久性。     

双价肾综合征出血热纯化疫苗的研究

目的　研制包含Ⅰ型和Ⅱ型病毒抗原的肾综合征出血热纯化疫苗 ,以提高疫苗质量及临床应用效果。方法　用金黄地鼠肾细胞培养的PS 6株 (Ⅰ型 )病毒和L99株 (Ⅱ型 )病毒以体积比 1∶1的比例配制成双价疫苗 ,经醋酸锌沉淀、超滤浓缩、Sepharose 4FF柱层析制备成双价纯化疫苗。结果　双价纯化疫苗经中国药品生物制品检定所检测 ,各项指标全部合格。疫苗于 37℃放置 2周和 4℃放置 3年 ,效力试验均合格。临床观察血清中和抗体阳转率大于 85 % ,仅出现 0 .5 %的轻反应。结论　研制的出血热双价纯化疫苗 ,各项质量指标均符合《双价肾综合征出血热纯化疫苗试行规程》的要求 ,临床应用效果良好     

HIV多表位核酸疫苗构建及其免疫原性

目的设计新型HIV复合多表位疫苗,并检测其在小鼠体内的免疫效果。方法检索抗原表位数据库,进行新型HIV多表位核酸疫苗的设计,利用化学合成的方法合成多表位基因,并构建重组质粒pVAX1-MEGNp24,转染BHK-21细胞,间接免疫荧光法检测多表位基因的表达。重组质粒免疫BALB/c小鼠,ELISA法检测抗体动态变化,流式细胞仪检测脾T淋巴细胞亚类。结果重组质粒pVAX1-MEGNp24经酶切及测序分析,证明构建正确。间接免疫荧光显示能在BHK-21细胞中表达多表位基因。免疫小鼠可诱导小鼠特异性体液免疫和细胞免疫。结论已成功构建了重组质粒pVAX1-MEGNp24,小鼠免疫试验显示其具有良好的免疫原性。