SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses.
SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses.
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DOI：
10.1016/j.xcrm.2021.100252
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发表时间：
2021-04-20
期刊：
影响因子：
--
通讯作者：
Murrell B
中科院分区：
文献类型：
--
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
SARS-CoV-2（严重急性呼吸综合征-冠状病毒-2）的爆发和传播是当前全球性的卫生紧急事件，迫切需要有效的预防疫苗。SARS-CoV-2的刺突糖蛋白介导进入宿主细胞，因此是中和抗体的靶标。在这里，我们表明，佐剂蛋白免疫与可溶性SARS-CoV-2刺突三聚体，稳定在融合前构象，在小鼠和恒河猴的结果在有效的抗体反应，中和抗体滴度超过那些通常测量的SARS-CoV-2血清阳性的人超过一个数量级。在单次给药后观察到中和抗体应答，在加强后达到异常高的滴度。监测恒河猴中中和抗体应答减弱的随访显示，在加强后至少4个月维持在高和稳定水平的持久应答。这些数据支持佐剂化SARS-CoV-2融合前稳定刺突蛋白亚单位疫苗的开发。在一次佐剂刺突蛋白免疫后可检测到中和抗体加强免疫产生比血清阳性人类供体中观察到的更高的中和滴度。在最后一次加强免疫后，中和抗体滴度保持高水平至少4个月。显示用佐剂化融合前稳定SARS-CoV-2刺突糖蛋白免疫在小鼠和猕猴中产生有效的抗体应答。一次免疫后可检测到中和抗体。加强导致异常的效力，中和滴度超过（> 10倍）在血清阳性人类中观察到的中和滴度，并且在4个月的随访期间保持高水平。
The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines. Neutralizing antibodies are detectable after one adjuvanted spike protein immunization Boosting yields higher neutralizing titers than observed in seropositive human donors Neutralizing antibody titers remain high for at least 4 months after the last boost Immunization stimulates spike-specific memory B cells Mandolesi et al. show that immunization with adjuvanted prefusion-stabilized SARS-CoV-2 spike glycoprotein yields potent antibody responses in mice and macaques. Neutralizing antibodies are detectable after one immunization. Boosting results in exceptional potency, with neutralizing titers exceeding (>10-fold) those observed in seropositive humans and remaining high during a 4-month follow-up.
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影响因子：
4.4
作者：
Cox MM;Patriarca PA;Treanor J
通讯作者：
Treanor J
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
DOI：
10.1177/2051013615595595
发表时间：
2015-07-01
期刊：
Therapeutic advances in vaccines
影响因子：
--
作者：
Cox, Manon M J;Izikson, Ruvim;Dunkle, Lisa
通讯作者：
Dunkle, Lisa
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：
5.5
作者：
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通讯作者：
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