接种基于重组水疱性口炎病毒的埃博拉疫苗（rVSVΔG-ZEBOV-GP）后对扎伊尔埃博拉糖蛋白和病毒载体蛋白的细胞和体液免疫。
Cellular and humoral immunity to Ebola Zaire glycoprotein and viral vector proteins following immunization with recombinant vesicular stomatitis virus-based Ebola vaccine (rVSVΔG-ZEBOV-GP).
机构信息
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Rm. 4-1479, MSC 1460, Bethesda, MD 20892, USA.
出版信息
Vaccine. 2023 Feb 17;41(8):1513-1523. doi: 10.1016/j.vaccine.2023.01.059. Epub 2023 Jan 31.
While effective at preventing Zaire ebolavirus (ZEBOV) disease, cellular immunity to ZEBOV and vector-directed immunity elicited by the recombinant vesicular stomatitis virus expressing ZEBOV glycoprotein (rVSVΔG-ZEBOV-GP) vaccine remain poorly understood. Sera and peripheral blood mononuclear cells were collected from 32 participants enrolled in a prospective multicenter study [ClinicalTrials.gov NCT02788227] before vaccination and up to six months post-vaccination. IgM and IgG antibodies, IgG-producing memory B cells (MBCs), and T cell reactivity to ZEBOV glycoprotein (ZEBOV-GP), vesicular stomatitis virus-Indiana strain (VSV-I) matrix (M) protein, and VSV-I nucleoprotein (NP) were measured using ELISA, ELISpot, and flow cytometry, respectively. 11/32 (34.4%) participants previously received a different investigational ZEBOV vaccine prior to enrollment and 21/32 (65.6%) participants were ZEBOV vaccine naïve. Both ZEBOV vaccine naïve and experienced participants had increased ZEBOV-GP IgG optical densities (ODs) post-rVSVΔG-ZEBOV-GP vaccination while only ZEBOV vaccine naïve participants had increased ZEBOV-GP IgM ODs. Transient IgM and IgG antibody responses to VSV-I M protein and NP were observed in a minority of participants. All participants had detectable ZEBOV-GP specific IgG-producing MBCs by 6 months post-vaccination while no changes were observed in the median IgG-producing MBCs to VSV-I proteins. T cell responses to ZEBOV-GP differed between ZEBOV vaccine experienced and ZEBOV vaccine naïve participants. T cell responses to both VSV-I M protein and VSV-I NP were observed, but were of a low magnitude. The rVSVΔG-ZEBOV-GP vaccine elicits robust humoral and memory B cell responses to ZEBOV glycoprotein in both ZEBOV vaccine naïve and experienced individuals and can generate vector-directed T cell immunity. Further research is needed to understand the significance of pre-existing vector and target antigen immunity on responses to booster doses of rVSVΔG-ZEBOV-GP and other rVSV-vectored vaccines.
虽然重组水疱性口炎病毒表达扎伊尔型埃博拉病毒糖蛋白（rVSVΔG-ZEBOV-GP）疫苗在预防扎伊尔型埃博拉病毒（ZEBOV）疾病方面非常有效，但针对 ZEBOV 的细胞免疫和载体导向免疫仍知之甚少。在这项前瞻性多中心研究[ClinicalTrials.gov NCT02788227]中，从 32 名参与者中收集了疫苗接种前和接种后 6 个月的血清和外周血单核细胞。使用酶联免疫吸附试验（ELISA）、酶联免疫斑点试验（ELISpot）和流式细胞术分别测量 IgM 和 IgG 抗体、产生 IgG 的记忆 B 细胞（MBC）以及针对 ZEBOV 糖蛋白（ZEBOV-GP）、水疱性口炎病毒印第安纳株（VSV-I）基质（M）蛋白和 VSV-I 核蛋白（NP）的 T 细胞反应。32 名参与者中有 11 名（34.4%）之前在入组前接受了另一种研究性 ZEBOV 疫苗，21 名（65.6%）参与者未接受 ZEBOV 疫苗。rVSVΔG-ZEBOV-GP 疫苗接种后，ZEBOV 疫苗接种经验丰富和无经验的参与者的 ZEBOV-GP IgG 光密度（OD）均增加，而只有 ZEBOV 疫苗无经验的参与者的 ZEBOV-GP IgM OD 增加。少数参与者观察到针对 VSV-I M 蛋白和 NP 的短暂 IgM 和 IgG 抗体反应。所有参与者在接种后 6 个月时均检测到可检测的 ZEBOV-GP 特异性 IgG 产生 MBC，而 VSV-I 蛋白的 IgG 产生 MBC 中位数没有变化。ZEBOV 疫苗接种经验丰富和无经验的参与者之间的 ZEBOV-GP T 细胞反应不同。观察到针对 VSV-I M 蛋白和 VSV-I NP 的 T 细胞反应，但反应幅度较低。rVSVΔG-ZEBOV-GP 疫苗在 ZEBOV 疫苗接种经验丰富和无经验的个体中均能诱导针对 ZEBOV 糖蛋白的强大体液和记忆 B 细胞反应，并能产生载体导向的 T 细胞免疫。需要进一步研究来了解针对 rVSVΔG-ZEBOV-GP 和其他 rVSV 载体疫苗加强剂量的预先存在的载体和靶抗原免疫对反应的意义。
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