Swart Maarten, Allen Jessica, Reed Brendan, Izquierdo Gil Ana, Verspuij Johan, Schmit-Tillemans Sonja, Chakkumkal Anish, Findeis Mark, Hafner Angela V, Harjivan Chandresh, Kurnat Rebecca, Kuipers Harmjan, Zahn Roland, Brandenburg Boerries
Johnson & Johnson, Janssen Vaccines & Prevention, 2333 CN Leiden, The Netherlands.
SaponiQx, 3 Forbes Road, Lexington, MA 02421, USA.
Vaccines (Basel). 2024 Dec 20;12(12):1435. doi: 10.3390/vaccines12121435.
Human metapneumovirus (HMPV) is a significant respiratory pathogen, particularly in vulnerable populations.
No vaccine for the prevention of HMPV is currently licensed, although several subunit vaccines are in development. Saponin-based adjuvant systems (AS), including QS-21, have transformed the field of subunit vaccines by dramatically increasing their potency and efficacy, leading to the development of several licensed vaccines. However, naturally sourced tree bark-extracted QS-21 faces supply and manufacturing challenges, hindering vaccine development.
This study reports on an alternative plant cell culture system for the consistent production of highly pure QS-21.
We evaluated the efficacy of cultured plant cell (cpc)-produced QS-21 in a novel HMPV vaccine, formulating a recombinant pre-fusion stabilized HMPV F protein (preF) with cpcQS-21 and a synthetic toll-like receptor 4 (TLR4) agonist adjuvant formulation.
In mice, TLR4 agonist containing adjuvant formulations with plant cell-produced QS-21 performed equally to licensed adjuvant AS01 containing tree-bark-extracted QS-21 and demonstrated a significant increase in immunogenicity against HMPV preF compared to the unadjuvanted control.
Our findings pave the way for a reliable, scalable, and sustainable source of pure QS-21, enabling the development of highly effective HMPV and other vaccines with significant public health impact.
人偏肺病毒（HMPV）是一种重要的呼吸道病原体，在易感人群中尤为如此。
目前尚无预防HMPV的疫苗获得许可，尽管有几种亚单位疫苗正在研发中。基于皂苷的佐剂系统（AS），包括QS-21，通过显著提高亚单位疫苗的效力和功效，改变了亚单位疫苗领域，促成了几种获得许可的疫苗的研发。然而，天然来源的树皮提取的QS-21面临供应和生产挑战，阻碍了疫苗的研发。
本研究报告了一种用于持续生产高纯度QS-21的替代植物细胞培养系统。
我们在一种新型HMPV疫苗中评估了培养植物细胞（cpc）产生的QS-21的功效，将cpcQS-21与一种合成的Toll样受体4（TLR4）激动剂佐剂配方一起配制重组预融合稳定化HMPV F蛋白（preF）。
在小鼠中，含有植物细胞产生的QS-21的含TLR4激动剂佐剂配方与含有树皮提取的QS-21的许可佐剂AS01表现相当，并且与未加佐剂的对照相比，对HMPV preF的免疫原性显著增加。
我们的研究结果为可靠、可扩展和可持续的纯QS-21来源铺平了道路，有助于开发对公共卫生有重大影响的高效HMPV疫苗和其他疫苗。
