作者: Zhao, Xuanna ; Wang, Weiming ; Zhang, Guilin ; Wu, Bin ; Xu, Youhua ; Geng, Kang ; Sun, Chaoqun ; Wu, Dong ; Huang, Wenbo ; Bai, Shuyou ; Chen, Min ; Zhao, Tingting ; Huang, Dan

Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.

Virology Journal

Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants

Article

作者: Pan, Hudan ; Huang, Bihong ; Liao, Guochao ; Chen, Liqing ; Li, Yebo ; Ke, Changwen ; Xu, Zeping ; Feng, Qian ; Liu, Jiangning ; Bao, Linlin ; Gao, Hongbin ; Li, Runze ; Zhu, Sisi ; Lau, Hungyan ; Qi, Xiaoxiao ; Wu, Miaoli ; Li, Dan ; Li, Chinyu ; Qin, Chuan ; Lv, Qi ; Liang, Shi ; Liang, Dan ; Deng, Xinyu ; Zhou, Hua ; Li, An'an ; Liu, Liang ; Zhu, Qing ; Fan, Xingxing ; Cong, Zhe ; Ke, Bixia ; Zhang, Yu ; Hong, Wenshan ; Liu, Zhongqiu ; Zhou, Feng ; Li, Yongchao

AbstractsThe COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.

项与 Guangdong Keguanda Pharmaceutical Technology Co., Ltd. 相关的新闻（医药）

2023-12-13

·生物制品圈

派真生物热烈祝贺克冠达研制“国内首款AAV疫苗”临床申请获CDE受理

在全球公共健康依然面临新冠病毒挑战的当下，克冠达医药自豪地宣布，其司自主研发的重组新型冠状病毒疫苗（AAV5载体）获中国药品监督管理局药品审评中心（CDE）正式受理进入临床开发。这是我国首款基于腺相关病毒（Adeno-associated virus，AAV）载体技术开发的疫苗，这一里程碑进展不仅体现了克冠达医药在生物医药领域的创新实力和引领地位，也标志着中国在疫苗研发领域取得了重大突破。派真生物对克冠达医药这一重要里程碑表示热烈地祝贺！AAV载体技术是近年来全球药物开发热点，但迄今未有AAV载体技术的疫苗产品上市，该技术在应用设计和产业化等方面的瓶颈一直是科学和产业界的重大挑战。克冠达医药研发团队凭借创新的技术平台、卓越的研发实力和不懈的创新追求，成功攻克了这些技术难题，使克冠达医药成为全球率先实现这一技术突破的医药企业，为全球疫苗开发带来了革命性进步。在临床前研究中，重组新型冠状病毒疫苗（AAV5载体）展现出了广谱性、高效性、长效性和优异的安全性，同时具备作为公众产品的高可及性，这些显著优势使该款技术路线疫苗在全球范围内极具竞争力，其具有克服其它技术路线新冠疫苗局限性的卓越临床应用价值，为人类终结新冠病毒的流行提供了全新策略。随着该款创新疫苗的产业化推进，克冠达医药的AAV载体技术平台展示了其在开发更多预防和治疗性疫苗以及药物方面的巨大潜力，这为克冠达医药多款AAV产品管线的开发提供了坚实基础。派真生物对于能够为克冠达医药这款突破性AAV疫苗项目提供专业的CMC服务，助力其开发国内首款AAV疫苗深感荣幸。在整个合作过程中，派真生物与克冠达团队共同努力，确保了服务质量的专业性和合规性和成果的高质量。我们为能参与这一具有里程碑意义的AAV疫苗开发项目感到自豪，并向克冠达医药取得的重大成就表示衷心的祝贺。展望未来，我们期待与克冠达医药持续合作，共同探索和开发更多创新的AAV产品，为医药领域带来更多突破。我们相信，通过双方的共同努力和技术创新，将会为全球公共健康事业做出更大的贡献。资料来源：1.公众号克冠达https://mp.weixin.qq.com/s/usjkdPITjNZbPWNF_MCU_w关于派真生物派真生物（PackGene）是一家专注于重组腺相关病毒（rAAV）载体包装的CRO & CTDMO科技公司, 为细胞与基因治疗(CGT)企业的重组AAV载体药物的早期研发、临床前开发、临床试验以及药物审批，提供快速、经济、高质量、规模化的一站式CMC解决方案。自2014年成立以来，作为AAV载体CRO服务领域的引领者，派真生物已经为20多个国家的客户提供上万批次的AAV定制样品，客户涵括全球顶级跨国制药公司与各类研究机构。在CTDMO服务领域，派真生物基于包括π-Alpha™293细胞AAV高产平台和π-Omega™质粒高产平台在内的五大技术平台，以完整的质量和分析体系，为药企AAV与质粒的GMP规模化生产需求提供合规服务。派真生物以“让老百姓用得起基因治疗”为使命，以加速创新基因药上市为己任，致力于成为全球基因药研发生产的长期合作伙伴。派真生物以创新技术作为发展的基础，以先进的载体生产技术以及突破性的载体工具两大方向为双轮驱动，来塑造派真生物在基因治疗领域CRO、CTDMO领域的国际品牌。联系我们：热线：400-835-0680 官网：www.packgene.cn邮箱：bd@packgene.com小派微信号：PackGene333微信公众号：派真生物、派真生物PackGene

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