Deng Lei, Wang Bao-Zhong
Center for Inflammation, Immunity & Infection , Georgia State University , 145 Piedmont Avenue SE , Atlanta , Georgia 30302-3965 , United States.
ACS Infect Dis. 2018 Dec 14;4(12):1656-1665. doi: 10.1021/acsinfecdis.8b00206. Epub 2018 Nov 15.
Annually recurring seasonal influenza causes massive economic loss and poses severe threats to public health worldwide. The current seasonal influenza vaccines are the most effective means of preventing influenza infections but possess major weaknesses. Seasonal influenza vaccines require annual updating of the vaccine strains. However, it is an unreachable task to accurately predict the future circulating strains. Vaccines with mismatched strains dramatically compromise the vaccine efficacy. In addition, the seasonal influenza vaccines are ineffective against an unpredictable pandemic. A universal influenza vaccine would overcome these weaknesses of the seasonal vaccines and abolish the threat of influenza pandemics. One approach under investigation is to design influenza vaccine immunogens based on conserved, type-specific amino acid sequences and conformational epitopes, rather than strain-specific. Such vaccines can elicit broadly reactive humoral and cellular immunity. Universal influenza vaccine development has intensively employed nanotechnology because the structural and morphological properties of nanoparticles dramatically improve vaccine immunogenicity and the induced immunity duration. Layered protein nanoparticles can decrease off-target immune responses, fine-tune antigen recognition and processing, and facilitate comprehensive immune response induction. Herein, we review the designs of effective nanoparticle universal influenza vaccines, the recent discoveries of specific nanoparticle features that contribute to immunogenicity enhancement, and recent progress in clinical trials.
每年复发的季节性流感会造成巨大的经济损失,并对全球公共卫生构成严重威胁。目前的季节性流感疫苗是预防流感感染的最有效手段,但存在重大缺陷。季节性流感疫苗需要每年更新疫苗毒株。然而,准确预测未来流行的毒株是一项无法完成的任务。毒株不匹配的疫苗会大大降低疫苗效力。此外,季节性流感疫苗对不可预测的大流行无效。通用流感疫苗将克服季节性疫苗的这些缺陷,并消除流感大流行的威胁。正在研究的一种方法是基于保守的、类型特异性的氨基酸序列和构象表位而非毒株特异性来设计流感疫苗免疫原。此类疫苗可引发广泛的体液免疫和细胞免疫。通用流感疫苗的研发大量采用了纳米技术,因为纳米颗粒的结构和形态特性可显著提高疫苗的免疫原性以及诱导免疫的持续时间。层状蛋白质纳米颗粒可减少非靶向免疫反应,微调抗原识别和加工过程,并促进全面免疫反应的诱导。在此,我们综述了有效的纳米颗粒通用流感疫苗的设计、有助于增强免疫原性的特定纳米颗粒特性的最新发现以及临床试验的最新进展。