Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice
Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice
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DOI：
10.1016/j.vaccine.2016.02.033
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发表时间：
2016-04-07
期刊：
影响因子：
5.5
通讯作者：
Smith, Gale
中科院分区：
文献类型：
--
作者：
Bengtsson, Karin Lovgren;Song, Haifeng;Smith, Gale
埃博拉病毒（EBOV）引起严重的出血热，目前尚无批准的治疗方法或预防疫苗。对EBOV疾病的保护性免疫的免疫学相关性尚不清楚。然而，非人灵长类动物研究表明，实验性疫苗的保护作用与EBOV糖蛋白（GP）以及EBOV GP特异性CD4（+）和CD8(+) T细胞的结合和中和抗体有关。本报告将2014年扎伊尔埃博拉病毒马科纳株（EBOV/Mak）未修饰的全长埃博拉病毒GP基因克隆到杆状病毒载体中。重组EBOV/Mak GP在Sf9昆虫细胞中以糖基化三聚体的形式产生，纯化后形成30-40 nm的球形颗粒。在小鼠中，通过病毒中和滴度和抗EBOV/Mak GP IgG检测，与AlPO4佐剂或非佐剂EBOV/Mak GP免疫相比，EBOV/Mak GP与皂苷佐剂Matrix-M共同给药的免疫原性显著增强。同样，含有Matrix-M的EBOV/Mak GP对分泌ifn - γ的抗原特异性T细胞的诱导作用最为显著。Matrix-M还以剂量依赖性的方式增强了脾脏中抗原特异性生发中心B细胞和滤泡辅助T细胞（T- fh）的频率。EBOV/Mak GP与Matrix-M结合免疫对致死性病毒攻击小鼠模型具有100%的保护作用；而AlPO4佐剂对EBOV/Mak GP抗原组小鼠无保护作用，仅10%（1/10）小鼠有保护作用。Matrix-M佐剂疫苗诱导特异性IgG和中和抗体的快速发作，增加了多功能CD4（+）和CD8(+) T细胞、特异性T- fh细胞、生发中心B细胞的频率，并在骨髓中持续存在EBOV gp特异性血浆B细胞。综上所述，在EBOV/Mak GP纳米颗粒中添加Matrix-M佐剂可增强B细胞和t细胞免疫刺激，这可能对具有广泛和持久保护性免疫的埃博拉亚单位疫苗至关重要。(C) 2016年作者。Elsevier Ltd.出版。
Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40 nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-gamma were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (T-FH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4(+) and CD8(+) T cells, specific T-FH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity. (C) 2016 The Authors. Published by Elsevier Ltd.