Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions.
Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions.
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DOI：
10.3389/fcimb.2023.1233148
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
克里米亚-刚果出血热病毒（CCHFV；内罗病毒科）是一种蜱传病原体，经常引起人类致命疾病。 CCHFV 地理分布广泛，非洲、亚洲、中东和欧洲均有病例报告。提供安全有效的疫苗对于流行国家限制疫情暴发和预防疾病至关重要。我们之前开发了一种病毒样复制子颗粒 (VRP) 疫苗，单剂量注射后，可为小鼠提供针对同源和异源致死性 CCHFV 攻击的完全保护。然而，这种疫苗引起的免疫反应尚未得到很好的表征，保护的相关性仍然未知。在这里，我们全面表征了 VRP 疫苗接种小鼠中细胞介导和体液免疫反应的动力学，并证明它们主要针对核蛋白 (NP)。 NP 抗体与中和活性的保护无关，但 VRP 疫苗接种会导致 NP 抗体具有 Fc 介导的抗体效应功能，例如补体激活 (ADCD) 和抗体介导的细胞吞噬作用 (ADCP)。这表明 Fc 介导的效应器功能可能有助于该疫苗的功效。
Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine’s efficacy.
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FC工程方法定义了针对埃博拉病毒的免疫力的功能体液相关性。
影响因子：
32.4
作者：
Gunn BM;Lu R;Slein MD;Ilinykh PA;Huang K;Atyeo C;Schendel SL;Kim J;Cain C;Roy V;Suscovich TJ;Takada A;Halfmann PJ;Kawaoka Y;Pauthner MG;Momoh M;Goba A;Kanneh L;Andersen KG;Schieffelin JS;Grant D;Garry RF;Saphire EO;Bukreyev A;Alter G
通讯作者：
Alter G
影响因子：
12.4
作者：
Hawman, David W.;Meade-White, Kimberly;Leventhal, Shanna;Appelberg, Sofia;Ahlen, Gustaf;Nikouyan, Negin;Clancy, Chad;Smith, Brian;Hanley, Patrick;Lovaglio, Jamie;Mirazimi, Ali;Sallberg, Matti;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
3.8
作者：
Kang SM;Compans RW
通讯作者：
Compans RW
影响因子：
5.4
作者：
Appelberg S;John L;Pardi N;Végvári Á;Bereczky S;Ahlén G;Monteil V;Abdurahman S;Mikaeloff F;Beattie M;Tam Y;Sällberg M;Neogi U;Weissman D;Mirazimi A
通讯作者：
Mirazimi A
影响因子：
5.5
作者：
Boshra, Hani;Lorenzo, Gema;Brun, Alejandro
通讯作者：
Brun, Alejandro