纳米载体
信使核糖核酸
穗蛋白
免疫系统
Spike(软件开发)
计算生物学
生物
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
2019年冠状病毒病(COVID-19)
病毒学
免疫学
医学
遗传学
计算机科学
药理学
基因
药品
软件工程
病理
传染病(医学专业)
疾病
作者
Laura Marcos-Villar,Beatriz Perdiguero,Shubaash Anthiya,Mireya L. Borrajo,Gustavo Lou,Lorenzo Franceschini,Ignasi Esteban,P.J. Sánchez-Cordón,Carmen Zamora,Carlos Óscar S. Sorzano,Luis Jordà,Laia Codó,Josep Lluis Gelpí,Marta Sisteré-Oró,Andreas Meyerhans,Kris Thielemans,Francisco Martínez-Jiménez,Nuria López-Vigas,Felipe García,Marı́a José Alonso,Montserrat Plana,Mariano Esteban,Carmen Elena Gómez
出处
期刊:npj vaccines
[Springer Nature]
日期:2024-03-06
卷期号:9 (1)
标识
DOI:10.1038/s41541-024-00838-8
摘要
Abstract Vaccines based on mRNA technology have revolutionized the field. In fact, lipid nanoparticles (LNP) formulated with mRNA are the preferential vaccine platform used in the fight against SARS-CoV-2 infection, with wider application against other diseases. The high demand and property right protection of the most potent cationic/ionizable lipids used for LNP formulation of COVID-19 mRNA vaccines have promoted the design of alternative nanocarriers for nucleic acid delivery. In this study we have evaluated the immunogenicity and efficacy of different rationally designed lipid and polymeric-based nanoparticle prototypes against SARS-CoV-2 infection. An mRNA coding for a trimeric soluble form of the receptor binding domain (RBD) of the spike (S) protein from SARS-CoV-2 was encapsulated using different components to form nanoemulsions (NE), nanocapsules (NC) and lipid nanoparticles (LNP). The toxicity and biological activity of these prototypes were evaluated in cultured cells after transfection and in mice following homologous prime/boost immunization. Our findings reveal good levels of RBD protein expression with most of the formulations. In C57BL/6 mice immunized intramuscularly with two doses of formulated RBD-mRNA, the modified lipid nanoparticle (mLNP) and the classical lipid nanoparticle (LNP-1) were the most effective delivery nanocarriers at inducing binding and neutralizing antibodies against SARS-CoV-2. Both prototypes fully protected susceptible K18-hACE2 transgenic mice from morbidity and mortality following a SARS-CoV-2 challenge. These results highlight that modulation of mRNAs immunogenicity can be achieved by using alternative nanocarriers and support further assessment of mLNP and LNP-1 prototypes as delivery vehicles for mRNA vaccines.
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