Vaccine Production Program, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9 West Watkins Mill Rd., Gaithersburg, MD, 20878, USA.
Twinbrook Imaging Facility, LIG, NIAID, NIH, Gaithersburg, MD, USA.
Sci Rep. 2024 Feb 24;14(1):4534. doi: 10.1038/s41598-024-54876-2.
Recent work by our laboratory and others indicates that co-display of multiple antigens on protein-based nanoparticles may be key to induce cross-reactive antibodies that provide broad protection against disease. To reach the ultimate goal of a universal vaccine for seasonal influenza, a mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for clinical trial (NCT04896086). FluMos-v1 is unique in that it is designed to co-display four recently circulating haemagglutinin (HA) strains; however, current vaccine analysis techniques are limited to nanoparticle population analysis, thus, are unable to determine the valency of an individual nanoparticle. For the first time, we demonstrate by total internal reflection fluorescence microscopy and supportive physical-chemical methods that the co-display of four antigens is indeed achieved in single nanoparticles. Additionally, we have determined percentages of multivalent (mosaic) nanoparticles with four, three, or two HA proteins. The integrated imaging and physicochemical methods we have developed for single nanoparticle multivalency will serve to further understand immunogenicity data from our current FluMos-v1 clinical trial.
我们实验室和其他实验室的最近研究表明,在基于蛋白质的纳米颗粒上共同展示多种抗原可能是诱导交叉反应性抗体的关键,这种抗体可以提供针对疾病的广泛保护。为了实现季节性流感通用疫苗的最终目标,我们开发了一种嵌合流感纳米颗粒疫苗(FluMos-v1)用于临床试验(NCT04896086)。FluMos-v1 的独特之处在于,它旨在共同展示四种最近流行的血凝素(HA)株;然而,当前的疫苗分析技术仅限于纳米颗粒群体分析,因此无法确定单个纳米颗粒的效价。我们首次通过全内反射荧光显微镜和支持性物理化学方法证明,确实可以在单个纳米颗粒中共同展示四种抗原。此外,我们还确定了具有四个、三个或两个 HA 蛋白的多价(嵌合)纳米颗粒的百分比。我们为单纳米颗粒多价性开发的综合成像和物理化学方法将有助于进一步理解我们目前 FluMos-v1 临床试验中的免疫原性数据。
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