Suppr超能文献

使用两种不同细胞系生产的铝盐佐剂 SARS-CoV-2 刺突铁蛋白纳米颗粒疫苗抗原的制剂开发和可比性研究。

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

作者信息

Kumru Ozan S, Sanyal Mrinmoy, Friedland Natalia, Hickey John, Joshi Richa, Weidenbacher Payton, Do Jonathan, Cheng Ya-Chen, Kim Peter S, Joshi Sangeeta B, Volkin David B

机构信息

Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS 66047, USA.

Department of Biochemistry, Stanford University School of Medicine, Palo Alto, CA, 94305 USA.

出版信息

bioRxiv. 2023 Apr 4:2023.04.03.535447. doi: 10.1101/2023.04.03.535447.

Abstract

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) performance in mice and (2) stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.

摘要

开发安全有效的第二代新冠疫苗以满足可负担性和储存稳定性要求,仍然是扩大全球疫苗接种覆盖率的重中之重。在本报告中,我们描述了一种自组装的新冠病毒刺突铁蛋白纳米颗粒疫苗抗原(称为DCFHP)的制剂开发和可比性研究,该抗原在两种不同的细胞系中生产,并与铝盐佐剂(氢氧化铝凝胶,AH)配制。不同水平的磷酸盐缓冲液改变了抗原-佐剂相互作用的程度和强度,并对这些制剂进行了以下评估:(1)在小鼠体内的性能,以及(2)稳定性概况。未添加佐剂的DCFHP产生的免疫反应极小,而添加AH佐剂的制剂引发的假病毒中和滴度大幅提高,与吸附到AH上的DCFHP抗原的约100%、约40%或约10%无关。然而,通过生物物理研究和用于测量与AH结合的抗原的ACE2受体结合的竞争性ELISA确定,这些制剂的稳定性特性有所不同。有趣的是,在4°C储存一个月后,观察到抗原性略有增加,同时抗原从AH上解吸的能力下降。最后,我们对在Expi293和CHO细胞中产生的DCFHP抗原进行了可比性评估,它们在N-连接寡糖谱上显示出预期的差异。尽管由不同的DCFHP糖型组成,但这两种制剂在关键质量属性方面高度相似,包括分子大小、结构完整性、构象稳定性、与ACE2受体的结合以及小鼠免疫原性概况。综上所述,这些研究支持未来对在CHO细胞中生产的添加AH佐剂的DCFHP候选疫苗进行临床前和临床开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a02e/10103975/70477f60896b/nihpp-2023.04.03.535447v1-f0001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验