Nature nanotechnology · 2025
Tailoring the adjuvanticity of lipid nanoparticles by PEG lipid ratio and phospholipid modifications.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Vadovics Máté, Zhao Wenchen, Daley Emily F, Lam Kieu, Daly Owen, Rashid Khalid, Lee Hailey R, Schreiner Petra, Lundgreen Kendall A, Gaudette Brian T, Shuvaev Vladimir V, Arguiri Evguenia, Muramatsu Hiromi, Sárközy András, Mdluli Thandiswa, Xu Junchao, Han Xuexiang, De Luna Nina, Castaño Diana, Bettini Emily, Ábrahám Edit, Lipinszki Zoltan, Carlucci Giuseppe, Bansode Avinash Haridas, Nguyen Katelyn, Le Thuc M, Luu Tony, Muzykantov Vladimir R, Bates Paul, Allman David, Mitchell Michael J, Locci Michela, Radu Caius G, Heyes James, Pardi Norbert
Аннотация
Lipid nanoparticles (LNPs) represent the leading delivery platform for mRNA vaccines with advantageous biocompatibility, scalability, adjuvant activity and often an acceptable safety profile. Here we investigate the physicochemical characteristics and adjuvanticity of four-component LNPs. Previous vaccine studies have demonstrated that altering the ionizable lipid influences the adjuvanticity of an LNP; however, the impact of the polyethylene glycol lipid and phospholipid has received less attention. Our mRNA-LNP vaccine formulations utilized different phospholipids and varying ratios of polyethylene glycol lipid, whereas the ionizable lipid and cholesterol remained approximately constant. We demonstrate that such modifications impact the magnitude and quality of the vaccine-elicited immune responses. We also dissect the underlying mechanisms and show that the biodistribution and cellular uptake of LNPs correlate with the magnitude and quality of the immune responses. These findings support the rational design of novel LNPs to tailor immune responses (cellular or humoral focused) based on the vaccine application.