Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens.
Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens.
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DOI：
10.1016/j.xcrm.2022.100780
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发表时间：
2022-10-18
影响因子：
14.3
通讯作者：
King, Neil P.
中科院分区：
文献类型：
--
作者：
Kraft, John C.;Pham, Minh N.;Shehata, Laila;Brinkkemper, Mitch;Boyoglu-Barnum, Seyhan;Sprouse, Kaitlin R.;Walls, Alexandra C.;Cheng, Suna;Murphy, Mike;Pettie, Deleah;Ahlrichs, Maggie;Sydeman, Claire;Johnson, Max;Blackstone, Alyssa;Ellis, Daniel;Ravichandran, Rashmi;Fiala, Brooke;Wrenn, Samuel;Miranda, Marcos;Sliepen, Kwinten;Brouwer, Philip J. M.;Antanasijevic, Aleksandar;Veesler, David;Ward, Andrew B.;Kanekiyo, Masaru;Pepper, Marion;Sanders, Rogier W.;King, Neil P.
蛋白质纳米颗粒支架越来越多地用于下一代疫苗设计，其中一些已经建立了临床安全性和有效性的记录。然而，纳米颗粒支架特异性的免疫应答如何影响展示抗原的免疫原性的规则尚未建立。在这里，我们定义的抗支架和抗原特异性抗体反应引起的蛋白质纳米颗粒免疫原之间的关系。我们报告说，通过物理掩蔽抑制抗支架反应不会增强抗原特异性抗体反应。在所有使用相同纳米颗粒支架但显示四种不同抗原的一系列免疫原中，只有HIV-1包膜糖蛋白（Env）对支架是次显性的。然而，我们也证明，支架特异性抗体反应可以竞争性地抑制抗原特异性反应时，支架提供过量。总的来说，我们的结果表明，抗支架抗体反应不太可能抑制蛋白纳米颗粒免疫原的抗原特异性抗体反应，其中抗原对支架具有免疫显性。支架的物理掩蔽不增强抗原（Ag）特异性抗体应答在一系列NP免疫原中，只有HIV-1 Env对支架是次显性的。支架特异性抗体应答可以竞争性抑制Ag特异性应答免疫显性Ag应答不太可能被支架应答抑制。定义由蛋白质纳米颗粒免疫原引发的抗支架和抗原特异性抗体应答之间的关系。总体而言，抗支架抗体应答不太可能抑制针对蛋白质纳米颗粒免疫原的抗原特异性抗体应答，其中抗原相对于支架是免疫显性的。
Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold. Physical masking of scaffolds does not enhance antigen (Ag)-specific antibody responses In a series of NP immunogens, only HIV-1 Env is subdominant to the scaffold Scaffold-specific antibody responses can competitively inhibit Ag-specific responses Immunodominant Ag responses are unlikely to be suppressed by scaffold responses Kraft et al. define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. Overall, anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.
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影响因子：
6.2
作者：
Falvo, Elisabetta;Tremante, Elisa;Ceci, Pierpaolo
通讯作者：
Ceci, Pierpaolo
影响因子：
5.4
作者：
Eggink, Dirk;Goff, Peter H.;Palese, Peter
通讯作者：
Palese, Peter
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
15.3
作者：
BRODY, NI;SISKIND, GW
通讯作者：
SISKIND, GW
DOI：
10.1126/science.1187816
发表时间：
2010-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bloom JD;Gong LI;Baltimore D
通讯作者：
Baltimore D