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针对 SARS-CoV-2 经多种途径给予脂质体包封的 mRNA 疫苗的研究。

The investigation of mRNA vaccines formulated in liposomes administrated in multiple routes against SARS-CoV-2.

机构信息

Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

J Control Release. 2021 Jul 10;335:449-456. doi: 10.1016/j.jconrel.2021.05.024. Epub 2021 May 21.

DOI:10.1016/j.jconrel.2021.05.024
PMID:34029632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8139338/
Abstract

COVID-19 pandemic has resulted in an unprecedented global public health crisis. It is obvious that SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Since obvious advantages including fast manufacturing speed, potent immunogenicity and good safety profile, six mRNA vaccines have been used to prevent SARS-CoV-2 infections in clinic with lipid nanoparticles (LNP) formulation via intramuscular injection. In this work, we first constructed RBD-encoding mRNA (RBD-mRNA) formulated in liposomes (LPX/RBD-mRNA) and investigated the influence of administration routes on the immunogenicity. LPX/RBD-mRNA can express RBD in vivo and successfully induced SARS-CoV-2 RBD specific antibodies in the vaccinated mice, which efficiently neutralized SARS-CoV-2 pseudotyped virus. Moreover, the administration routes were found to affect the virus neutralizing capacity of sera derived from the immunized mice and the types (Th1-type and Th2-type) of cellular immune responses. This study indicated that liposome-based RBD-mRNA vaccine with optimal administration route might be a potential candidate against SARS-CoV-2 infection with good efficacy and safety.

摘要

新型冠状病毒肺炎大流行导致了一场史无前例的全球公共卫生危机。显然，需要 SARS-CoV-2 疫苗来控制全球 COVID-19 公共卫生危机。由于具有快速制造速度、强大的免疫原性和良好的安全性等明显优势，六种 mRNA 疫苗已通过肌肉内注射脂质纳米粒（LNP）制剂用于预防 SARS-CoV-2 感染。在这项工作中，我们首先构建了包封在脂质体（LPX/RBD-mRNA）中的 RBD 编码 mRNA（RBD-mRNA），并研究了给药途径对免疫原性的影响。LPX/RBD-mRNA 可在体内表达 RBD，并成功诱导接种小鼠产生 SARS-CoV-2 RBD 特异性抗体，该抗体能有效中和 SARS-CoV-2 假型病毒。此外，还发现给药途径会影响免疫小鼠血清的病毒中和能力以及细胞免疫应答的类型（Th1 型和 Th2 型）。这项研究表明，基于脂质体的 RBD-mRNA 疫苗与最佳给药途径相结合，可能是一种具有良好疗效和安全性的针对 SARS-CoV-2 感染的潜在候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/d0f2798b3529/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/f212bf5ca3f1/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/6a5dd658046d/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/7e54a78090a7/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/05b9ac79f07b/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/fb2773d13ff2/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/2a453b3c3b75/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/407478d31409/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/4344203729ab/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/c32bb148f7f0/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/d0f2798b3529/gr9_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/f212bf5ca3f1/ga1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/6a5dd658046d/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/7e54a78090a7/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/05b9ac79f07b/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/fb2773d13ff2/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/2a453b3c3b75/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/407478d31409/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/4344203729ab/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/c32bb148f7f0/gr8_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3cf/8139338/d0f2798b3529/gr9_lrg.jpg

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