Tweet
Sci Adv
. 2022 Nov 25;8(47):eabo1827.
doi: 10.1126/sciadv.abo1827. Epub 2022 Nov 23.
Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses
Yingying Shi 1 2 , Jiaxin Huang 2 , Yu Liu 2 , Jing Liu 1 , Xuemeng Guo 2 , Jianhua Li 3 , Liming Gong 3 , Xin Zhou 4 , Guofeng Cheng 4 , Yunqing Qiu 1 , Jian You 1 2 , Yan Lou 1
Affiliations
- PMID: 36417530
- DOI: 10.1126/sciadv.abo1827
Abstract
The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical characteristics of nanoparticles shaped their tissue dissemination, cellular uptake, and intracellular trafficking, which eventually determined the activation of antiviral humoral and cellular immunity. Specifically, LNP was mainly internalized by myocyte and subsequently circumvented lysosome degradation, giving rise to humoral-biased immune responses. Meanwhile, CNE and Lipo induced cellular-preferred immunity, which was respectively attributed to the better lysosomal escape in dendritic cells and the superior biodistribution in secondary lymphoid organs. Overall, this study may guide the design and clinical use of mRNA vaccines against COVID-19.