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流感病毒感染后佐剂疫苗诱导的发病机制。

An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection.

作者信息

Hsu Shiou-Chih, Lin Kun-Hsien, Tseng Yung-Chieh, Cheng Yang-Yu, Ma Hsiu-Hua, Chen Ying-Chun, Jan Jia-Tsrong, Wu Chung-Yi, Ma Che

机构信息

Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115201, Taiwan.

Institute of Cellular and Organismic Biology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115201, Taiwan.

出版信息

Vaccines (Basel). 2024 May 23;12(6):569. doi: 10.3390/vaccines12060569.

Abstract

An incomplete Freund's adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses.

摘要

不完全弗氏佐剂在经鼻接种A/加利福尼亚/07/2009(H1N1)病毒后,在接种疫苗的小鼠中引发了明显的发病机制,尽管其诱导的特异性抗体滴度高于其他佐剂配方。氢氧化铝佐剂在与糖脂的各种配方中均未引发任何致病迹象。一种糖脂,α-半乳糖神经酰胺,增强了不同佐剂配方对甲型流感抗体反应的刺激作用。与其合成类似物C34相比,α-半乳糖神经酰胺对氢氧化铝佐剂对特异性抗体反应的刺激作用具有拮抗作用。单独使用氢氧化铝佐剂可提供完全的疫苗诱导保护,防止由同一株甲型流感病毒的致死性攻击导致的死亡和发病。研究结果表明,佐剂可以重塑免疫反应,要么改善疫苗诱导的免疫力,要么引发意想不到的致病后果。基于这些观察结果,本研究意味着开发一种精确佐剂以实现无害接种的重要性,旨在产生保护性免疫而无异常反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1684/11209567/a17a7b22d54a/vaccines-12-00569-g001.jpg

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