Intranasal Immunization with Liposome-Displayed Receptor-Binding Domain Induces Mucosal Immunity and Protection against SARS-CoV-2.
Intranasal Immunization with Liposome-Displayed Receptor-Binding Domain Induces Mucosal Immunity and Protection against SARS-CoV-2.
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DOI：
10.3390/pathogens11091035
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发表时间：
2022-09-12
期刊：
影响因子：
--
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由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的全球大流行促使人们努力开发有效的疫苗方法。目前，批准的2019年冠状病毒病(新冠肺炎)疫苗是通过肌肉注射(I.M.)接种的。路线。在这里，我们证明了SARS-CoV-2尖峰(S)糖蛋白受体结合域(RBD)，当展示在免疫原脂质体上时，可以经鼻腔(I.N.)给药后，可在肺部产生抗原特异性的IgA和抗原特异性的细胞反应。免疫后，肺部的抗原提呈细胞摄取了显示RBD的脂质体。用亚微克剂量的RBD脂质体免疫K18人ACE2转基因小鼠，然后用SARS-CoV-2攻击K18人ACE2转基因小鼠，在感染的早期过程中病毒载量减少，IM实现了病毒的完全清除。然而，这两种疫苗接种途径都导致了对致死性病毒感染的完全保护，显示了进一步探索和优化脂质体展示的抗原疫苗免疫的潜力。
The global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to efforts in developing effective vaccine approaches. Currently, approved coronavirus disease 2019 (COVID-19) vaccines are administered through an intramuscular (I.M.) route. Here, we show that the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD), when displayed on immunogenic liposomes, can be intranasally (I.N.) administered, resulting in the production of antigen-specific IgA and antigen-specific cellular responses in the lungs. Following I.N. immunization, antigen-presenting cells of the lungs took up liposomes displaying the RBD. K18 human ACE2-transgenic mice that were immunized I.M or I.N with sub-microgram doses of RBD liposomes and that were then challenged with SARS-CoV-2 had a reduced viral load in the early course of infection, with I.M. achieving complete viral clearance. Nevertheless, both vaccine administration routes led to full protection against lethal viral infection, demonstrating the potential for the further exploration and optimization of I.N immunization with liposome-displayed antigen vaccines.
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影响因子：
82.9
作者：
Li J;Hou L;Guo X;Jin P;Wu S;Zhu J;Pan H;Wang X;Song Z;Wan J;Cui L;Li J;Chen Y;Wang X;Jin L;Liu J;Shi F;Xu X;Zhu T;Chen W;Zhu F
通讯作者：
Zhu F
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
DOI：
10.1056/nejmoa2105290
发表时间：
2021-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Falsey AR;Sobieszczyk ME;Hirsch I;Sproule S;Robb ML;Corey L;Neuzil KM;Hahn W;Hunt J;Mulligan MJ;McEvoy C;DeJesus E;Hassman M;Little SJ;Pahud BA;Durbin A;Pickrell P;Daar ES;Bush L;Solis J;Carr QO;Oyedele T;Buchbinder S;Cowden J;Vargas SL;Guerreros Benavides A;Call R;Keefer MC;Kirkpatrick BD;Pullman J;Tong T;Brewinski Isaacs M;Benkeser D;Janes HE;Nason MC;Green JA;Kelly EJ;Maaske J;Mueller N;Shoemaker K;Takas T;Marshall RP;Pangalos MN;Villafana T;Gonzalez-Lopez A;AstraZeneca AZD1222 Clinical Study Group
通讯作者：
AstraZeneca AZD1222 Clinical Study Group
影响因子：
168.9
作者：
Chan, Jasper Fuk-Woo;Yuan, Shuofeng;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
9.2
作者：
Huang, Wei-Chiao;Deng, Bingbing;Lovell, Jonathan F.
通讯作者：
Lovell, Jonathan F.