Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles.
Developing Next-Generation Protein-Based Vaccines Using High-Affinity Glycan Ligand-Decorated Glyconanoparticles.
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DOI：
10.1002/advs.202204598
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发表时间：
2023-01
期刊：
影响因子：
--
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Gao Y;Wang W;Yang Y;Zhao Q;Yang C;Jia X;Liu Y;Zhou M;Zeng W;Huang X;Chiu S;Jin T;Wu X
癌症和COVID-19等重大疾病是令人恐惧的全球健康问题，必须采取持续行动开发疫苗。在此，首次将乙氧基缩醛化葡聚糖纳米颗粒（Ace-Dex-NP）用靶向巨噬细胞的9-N-（4 H-噻吩并[3，2-c]色烯-2-氨基甲酰基）-Siaα2 - 3Galβ1 - 4GlcNAc（TCCSia-LacNAc）官能化，作为通用疫苗设计平台。首先，合成含叠氮化物的氧化Ace-Dex-NP。在NP与卵清蛋白（OVA）和瑞喹莫特（Rd）缀合后，它们与TCCSia-LacNAc-DBCO偶联以产生TCCSia-Ace-Dex-OVA-Rd，其诱导有效的、持久的OVA特异性细胞毒性T淋巴细胞（CTL）应答和高抗OVA IgG，为小鼠提供针对肿瘤的上级保护。接下来，这种策略被用于开发针对严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）感染的疫苗。SARS-CoV-2刺突蛋白的受体结合结构域（RBD）是中和抗体的主要靶点。TCCSia‐Ace‐Dex平台优先用于设计基于RBD的疫苗。引人注目的是，合成的TCCSia-Ace-Dex-RBD-Rd引发了针对活的SARS-CoV-2感染的Vero E6细胞的有效的RBD-中和抗体。为了开发通用的SARS-CoV-2疫苗，还制备了携带SARS-CoV-2核衣壳蛋白（N）的TCCSia-Ace-Dex-N-Rd疫苗，该蛋白在SARS-CoV-2及其相关变体（VOCs）中高度保守，包括Omicron（BA.1至BA.5）;该疫苗可针对感染SARS-CoV-2及其VOCs的靶细胞引发强烈的N-特异性CTL应答。通过将蛋白质抗原（PA）、瑞喹莫特（Rd）和9-N-（4 H-噻吩并[3，2-c]色烯-2-氨基甲酰基）-Siaα2 - 3Galβ1 - 4GlcNAcβPro-DBCO（TCCSia-LacNAc-DBCO）与部分氧化的叠氮化物展示乙氧基缩醛化葡聚糖（Oxi-Ace-Dex-Az）纳米颗粒顺序缀合，开发了通用的TCCSia-Ace-Dex-PA-Rd平台。这种新型平台已成功应用于开发下一代基于蛋白质的癌症疫苗，严重急性呼吸道综合征冠状病毒-2（SARS-CoV-2）及其相关变体（VOC）。
Major diseases, such as cancer and COVID‐19, are frightening global health problems, and sustained action is necessary to develop vaccines. Here, for the first time, ethoxy acetalated dextran nanoparticles (Ace‐Dex‐NPs) are functionalized with 9‐N‐(4H‐thieno[3,2‐c]chromene‐2‐carbamoyl)‐Siaα2−3Galβ1−4GlcNAc (TCCSia‐LacNAc) targeting macrophages as a universal vaccine design platform. First, azide‐containing oxidized Ace‐Dex‐NPs are synthesized. After the NPs are conjugated with ovalbumin (OVA) and resiquimod (Rd), they are coupled to TCCSia‐LacNAc‐DBCO to produce TCCSia‐Ace‐Dex‐OVA‐Rd, which induce a potent, long‐lasting OVA‐specific cytotoxic T‐lymphocyte (CTL) response and high anti‐OVA IgG, providing mice with superior protection against tumors. Next, this strategy is exploited to develop vaccines against infection by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein is the main target for neutralizing antibodies. The TCCSia‐Ace‐Dex platform is preferentially used for designing an RBD‐based vaccine. Strikingly, the synthetic TCCSia‐Ace‐Dex‐RBD‐Rd elicited potent RBD‐neutralizing antibodies against live SARS‐CoV‐2 infected Vero E6 cells. To develop a universal SARS‐CoV‐2 vaccine, the TCCSia‐Ace‐Dex‐N‐Rd vaccine carrying SARS‐CoV‐2 nucleocapsid protein (N) is also prepared, which is highly conserved among SARS‐CoV‐2 and its variants of concern (VOCs), including Omicron (BA.1 to BA.5); this vaccine can trigger strong N‐specific CTL responses against target cells infected with SARS‐CoV‐2 and its VOCs. By sequentially conjugating a protein antigen (PA), resiquimod (Rd), and 9‐N‐(4H‐thieno[3,2‐c]chromene‐2‐carbamoyl)‐Siaα2‐3Galβ1‐4GlcNAcβPro‐DBCO (TCCSia‐LacNAc‐DBCO) with partially oxidized azide‐displaying ethoxy acetalated dextran (Oxi‐Ace‐Dex‐Az) nanoparticles, a versatile TCCSia‐Ace‐Dex‐PA‐Rd platform is developed. This novel platform has been successfully applied to develop next‐generation protein‐based vaccines against cancer, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) and its variants of concern (VOCs).
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影响因子：
64.5
作者：
Cevik M;Grubaugh ND;Iwasaki A;Openshaw P
通讯作者：
Openshaw P
影响因子：
14
作者：
Gao Y;Zhao Q;Xiao M;Huang X;Wu X
通讯作者：
Wu X
DOI：
10.1056/nejmoa2107659
发表时间：
2021-09-23
期刊：
The New England journal of medicine
影响因子：
--
作者：
Heath PT;Galiza EP;Baxter DN;Boffito M;Browne D;Burns F;Chadwick DR;Clark R;Cosgrove C;Galloway J;Goodman AL;Heer A;Higham A;Iyengar S;Jamal A;Jeanes C;Kalra PA;Kyriakidou C;McAuley DF;Meyrick A;Minassian AM;Minton J;Moore P;Munsoor I;Nicholls H;Osanlou O;Packham J;Pretswell CH;San Francisco Ramos A;Saralaya D;Sheridan RP;Smith R;Soiza RL;Swift PA;Thomson EC;Turner J;Viljoen ME;Albert G;Cho I;Dubovsky F;Glenn G;Rivers J;Robertson A;Smith K;Toback S;2019nCoV-302 Study Group
通讯作者：
2019nCoV-302 Study Group
DOI：
10.1056/nejmoa2119451
发表时间：
2022-04-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Andrews N;Stowe J;Kirsebom F;Toffa S;Rickeard T;Gallagher E;Gower C;Kall M;Groves N;O'Connell AM;Simons D;Blomquist PB;Zaidi A;Nash S;Iwani Binti Abdul Aziz N;Thelwall S;Dabrera G;Myers R;Amirthalingam G;Gharbia S;Barrett JC;Elson R;Ladhani SN;Ferguson N;Zambon M;Campbell CNJ;Brown K;Hopkins S;Chand M;Ramsay M;Lopez Bernal J
通讯作者：
Lopez Bernal J
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