Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.
Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.
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DOI：
10.1016/j.celrep.2023.112391
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发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
亚单位疫苗通常需要与佐剂共同接种以诱导保护性免疫，这增加了可能阻碍快速大流行反应的开发障碍。为了避免严重急性呼吸综合征冠状病毒2(SARS-CoV-2)亚单位疫苗中佐剂的需要，我们设计了一种耐热免疫靶向疫苗(ITV)，它利用泛人类白细胞抗原DR单抗44H10将病毒刺突蛋白受体结合域(RBD)递送到抗原提呈细胞。X射线结晶学分析表明，44H10与人类白细胞抗原DR上的一个保守表位结合，为其具有广泛的人类白细胞抗原DR反应性提供了基础。兔和雪貂的无佐剂ITV免疫诱导了强大的抗RBD抗体反应，中和了令人担忧的SARS-CoV-2变种，保护了受体免受SARS-CoV-2的攻击。我们证明，ITV支架相对于辅助T细胞表位和不同的RBD抗原的模块化性质有助于广泛的肉瘤病毒中和。我们的发现支持抗人类白细胞抗原-DR免疫靶向作为一种有效的手段，在不需要佐剂的情况下诱导对亚单位抗原的强烈抗体反应。Kassardkin等人。设计并鉴定一种模块化疫苗支架，用于将抗原输送到抗原呈递细胞上的MHC II类。这种蛋白疫苗诱导广泛的肉瘤病毒中和抗体反应，并独立于佐剂联合接种而保护免受SARS-CoV-2病毒攻击。
Subunit vaccines typically require co-administration with an adjuvant to elicit protective immunity, adding development hurdles that can impede rapid pandemic responses. To circumvent the need for adjuvant in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine, we engineer a thermostable immunotargeting vaccine (ITV) that leverages the pan-HLA-DR monoclonal antibody 44H10 to deliver the viral spike protein receptor-binding domain (RBD) to antigen-presenting cells. X-ray crystallography shows that 44H10 binds to a conserved epitope on HLA-DR, providing the basis for its broad HLA-DR reactivity. Adjuvant-free ITV immunization in rabbits and ferrets induces robust anti-RBD antibody responses that neutralize SARS-CoV-2 variants of concern and protect recipients from SARS-CoV-2 challenge. We demonstrate that the modular nature of the ITV scaffold with respect to helper T cell epitopes and diverse RBD antigens facilitates broad sarbecovirus neutralization. Our findings support anti-HLA-DR immunotargeting as an effective means to induce strong antibody responses to subunit antigens without requiring an adjuvant. Kassardjian et al. engineer and characterize a modular vaccine scaffold for the delivery of antigen to MHC class II on antigen-presenting cells. This protein vaccine induces broad sarbecovirus neutralizing antibody responses and protects from SARS-CoV-2 viral challenge independently of adjuvant co-administration.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
4.4
作者：
Grodeland, Gunnveig;Fredriksen, Agnete Brunsvik;Bogen, Bjarne
通讯作者：
Bogen, Bjarne
影响因子：
30.3
作者：
Evans, John P.;Zeng, Cong;Qu, Panke;Faraone, Julia;Zheng, Yi-Min;Carlin, Claire;Bednash, Joseph S.;Zhou, Tongqing;Lozanski, Gerard;Mallampalli, Rama;Saif, Linda J.;Oltz, Eugene M.;Mohler, Peter J.;Xu, Kai;Gumina, Richard J.;Liu, Shan-Lu
通讯作者：
Liu, Shan-Lu
影响因子：
8
作者：
Abe, Kento T.;Li, Zhijie;Gingras, Anne-Claude
通讯作者：
Gingras, Anne-Claude
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