ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge.
ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects guinea pigs against lethal Lassa virus challenge.
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DOI：
10.1038/s41541-021-00291-x
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发表时间：
2021-03-02
期刊：
影响因子：
9.2
通讯作者：
Munster VJ
中科院分区：
文献类型：
--
作者：
Fischer RJ;Purushotham JN;van Doremalen N;Sebastian S;Meade-White K;Cordova K;Letko M;Jeremiah Matson M;Feldmann F;Haddock E;LaCasse R;Saturday G;Lambe T;Gilbert SC;Munster VJ
拉沙病毒（LASV）每年感染数十万人，这突出表明需要加速开发预防，诊断和治疗干预措施。迄今为止，还没有LASV疫苗获得许可。ChAdOx 1-Lassa-GPC是一种黑猩猩腺病毒载体疫苗，编码Josiah株LASV糖蛋白前体（GPC）基因。在下面的研究中，我们表明ChAdOx 1-Lassa-GPC是免疫原性的，在小鼠中诱导强大的T细胞和抗体应答。此外，单次剂量的ChAdOx 1-Lassa-GPC完全保护Hartley豚鼠在用豚鼠适应性LASV（毒株Josiah）致死性攻击后免于发病和死亡。相比之下，对照接种动物在感染后10-12天达到安乐死标准。在接种动物的组织中检测到有限量的LASV RNA。仅在接受单剂量疫苗的1只动物中检出活LASV。ChAdOx 1-Lassa-GPC在豚鼠中的初免-加强方案显著增加了抗原特异性抗体滴度，并从组织中清除了活的LASV。这些数据支持ChAdOx 1-Lassa-GPC的进一步开发和在非人灵长类动物感染模型中的测试。
Lassa virus (LASV) infects hundreds of thousands of individuals each year, highlighting the need for the accelerated development of preventive, diagnostic, and therapeutic interventions. To date, no vaccine has been licensed for LASV. ChAdOx1-Lassa-GPC is a chimpanzee adenovirus-vectored vaccine encoding the Josiah strain LASV glycoprotein precursor (GPC) gene. In the following study, we show that ChAdOx1-Lassa-GPC is immunogenic, inducing robust T-cell and antibody responses in mice. Furthermore, a single dose of ChAdOx1-Lassa-GPC fully protects Hartley guinea pigs against morbidity and mortality following lethal challenge with a guinea pig-adapted LASV (strain Josiah). By contrast, control vaccinated animals reached euthanasia criteria 10–12 days after infection. Limited amounts of LASV RNA were detected in the tissues of vaccinated animals. Viable LASV was detected in only one animal receiving a single dose of the vaccine. A prime-boost regimen of ChAdOx1-Lassa-GPC in guinea pigs significantly increased antigen-specific antibody titers and cleared viable LASV from the tissues. These data support further development of ChAdOx1-Lassa-GPC and testing in non-human primate models of infection.
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影响因子：
9.2
作者：
Fischer RJ;Purushotham JN;van Doremalen N;Sebastian S;Meade-White K;Cordova K;Letko M;Jeremiah Matson M;Feldmann F;Haddock E;LaCasse R;Saturday G;Lambe T;Gilbert SC;Munster VJ
通讯作者：
Munster VJ
影响因子：
6.7
作者：
Flatz L;Rieger T;Merkler D;Bergthaler A;Regen T;Schedensack M;Bestmann L;Verschoor A;Kreutzfeldt M;Brück W;Hanisch UK;Günther S;Pinschewer DD
通讯作者：
Pinschewer DD
影响因子：
5.4
作者：
JAHRLING, PB;PETERS, CJ
通讯作者：
PETERS, CJ
影响因子：
--
作者：
FISHERHOCH, SP;TOMORI, O;MCCORMICK, JB
通讯作者：
MCCORMICK, JB
DOI：
10.1016/j.ymthe.2016.11.003
发表时间：
2017-02-01
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Bliss CM;Drammeh A;Bowyer G;Sanou GS;Jagne YJ;Ouedraogo O;Edwards NJ;Tarama C;Ouedraogo N;Ouedraogo M;Njie-Jobe J;Diarra A;Afolabi MO;Tiono AB;Yaro JB;Adetifa UJ;Hodgson SH;Anagnostou NA;Roberts R;Duncan CJ;Cortese R;Viebig NK;Leroy O;Lawrie AM;Flanagan KL;Kampmann B;Imoukhuede EB;Sirima SB;Bojang K;Hill AV;Nébié I;Ewer KJ
通讯作者：
Ewer KJ