Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.
Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.
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DOI：
10.1126/sciadv.abj1476
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发表时间：
2021-12-03
期刊：
影响因子：
13.6
通讯作者：
Lovell J
中科院分区：
文献类型：
--
作者：
Mabrouk MT;Chiem K;Rujas E;Huang WC;Jahagirdar D;Quinn B;Surendran Nair M;Nissly RH;Cavener VS;Boyle NR;Sornberger TA;Kuchipudi SV;Ortega J;Julien JP;Martinez-Sobrido L;Lovell J
展示在脂质体上的SARS-CoV-2抗原是耐热的，可以保护小鼠免受致命病毒的攻击。新冠肺炎大流行激发了人们对高效、耐热的SARS-CoV-2疫苗的兴趣。在这里，我们评估了用重组SARS-CoV-2抗原修饰的冷冻干燥纳米颗粒的低剂量免疫。将SARS-CoV-2刺突糖蛋白或其受体结合域(RbD；小鼠疫苗剂量，0.1μg)展示在脂质体上，脂质体中含有颗粒诱导型脂质：钴卟啉磷脂(剂量，0.4μg)、单磷酰脂A(剂量，0.16μg)和QS-21(剂量，0.16μg)。经过冷冻干燥条件的优化，SPEKE或RBD修饰的脂质体在60℃下以冷冻干燥而不是液体形式储存时，可以有效地重组并保持与人血管紧张素转换酶2(HACE2)结合的构象能力至少一周。用重组疫苗配方对hACE2转基因小鼠进行Prime-Boost肌肉接种，可产生有效的抗体反应，抑制RBD与hACE2的结合，并中和假型和活的SARS-CoV-2。病毒攻击两天后，免疫的转基因小鼠清除了病毒，并完全免受致命疾病的影响。
SARS-CoV-2 antigens that are displayed on liposomes and lyophilized are thermostable and protect mice from lethal virus challenge. The COVID-19 pandemic has spurred interest in potent and thermostable SARS-CoV-2 vaccines. Here, we assess low-dose immunization with lyophilized nanoparticles decorated with recombinant SARS-CoV-2 antigens. The SARS-CoV-2 Spike glycoprotein or its receptor-binding domain (RBD; mouse vaccine dose, 0.1 μg) was displayed on liposomes incorporating a particle-inducing lipid, cobalt porphyrin-phospholipid (dose, 0.4 μg), along with monophosphoryl lipid A (dose, 0.16 μg) and QS-21 (dose, 0.16 μg). Following optimization of lyophilization conditions, Spike or RBD-decorated liposomes were effectively reconstituted and maintained conformational capacity for binding human angiotensin-converting enzyme 2 (hACE2) for at least a week when stored at 60°C in lyophilized but not liquid format. Prime-boost intramuscular vaccination of hACE2-transgenic mice with the reconstituted vaccine formulations induced effective antibody responses that inhibited RBD binding to hACE2 and neutralized pseudotyped and live SARS-CoV-2. Two days following viral challenge, immunized transgenic mice cleared the virus and were fully protected from lethal disease.
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DOI：
10.3390/v13010082
发表时间：
2021-01-08
期刊：
Viruses
影响因子：
--
作者：
Oommen A;Cunningham S;Joshi L
通讯作者：
Joshi L
DOI：
10.1016/j.xcrm.2021.100252
发表时间：
2021-04-20
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Mandolesi M;Sheward DJ;Hanke L;Ma J;Pushparaj P;Perez Vidakovics L;Kim C;Àdori M;Lenart K;Loré K;Castro Dopico X;Coquet JM;McInerney GM;Karlsson Hedestam GB;Murrell B
通讯作者：
Murrell B
影响因子：
38.3
作者：
Huang WC;Deng B;Lin C;Carter KA;Geng J;Razi A;He X;Chitgupi U;Federizon J;Sun B;Long CA;Ortega J;Dutta S;King CR;Miura K;Lee SM;Lovell JF
通讯作者：
Lovell JF
影响因子：
6.2
作者：
Sauer, SW;Keim, ME
通讯作者：
Keim, ME
影响因子：
4.1
作者：
Renkema, JMS;Lakemond, CMM;van Vliet, T
通讯作者：
van Vliet, T