Phase I trial of a CD8+ T-Cell peptide epitope-based vaccine for infectious mononucleosis
Phase I trial of a CD8+ T-Cell peptide epitope-based vaccine for infectious mononucleosis
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DOI：
10.1128/jvi.01409-07
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发表时间：
2008-02-01
影响因子：
5.4
通讯作者：
Bharadwaj, Mandvi
中科院分区：
文献类型：
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作者：
Elliott, Suzanne L.;Suhrbier, Andreas;Bharadwaj, Mandvi
在14名HLA B*0801阳性、EB病毒（EBV）血清阴性成人中进行了一项针对传染性单核细胞增多症的CD 8（+）T细胞肽表位疫苗的单盲、随机、安慰剂对照、单中心I期临床试验。该疫苗包含在油包水佐剂Montanide伊萨720中配制的HLA B*0801限制性肽表位FLRGR AYGL和破伤风类毒素。通过γ干扰素酶联免疫斑点试验和/或有限稀释分析，在8/9例肽疫苗接种者和0/4例安慰剂疫苗接种者中检测到FLRGRAYGL特异性应答。在大多数EBV血清阳性个体的FLRGRAYGL特异性T细胞中发现的相同T细胞受体V β CDR 3序列也可以在疫苗接受者的外周血中检测到。疫苗耐受性良好，主要副作用为轻度至中度注射部位反应。在2- 1/2年的随访后，1/2获得EBV的安慰剂疫苗接种者发展为传染性单核细胞增多症，而4/4在完成肽疫苗接种后获得EBV的疫苗接种者无症状地血清转化。单表位疫苗接种不会使个体易患疾病，也不会显著影响血清转换后EBV特异性CD 8（+）T细胞反应的正常库的发展。
A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8(+) T-cell peptide epitope vaccine against infectious mononucleosis was conducted with 14 HLA B*0801-positive, Epstein-Barr virus (EBV)-seronegative adults. The vaccine comprised the HLA B*0801-restricted peptide epitope FLRGR AYGL and tetanus toxoid formulated in a water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected in 8/9 peptide-vaccine recipients and 0/4 placebo vaccine recipients by gamma interferon enzyme-linked immunospot assay and/or limiting-dilution analysis. The same T-cell receptor V beta CDR3 sequence that is found in FLRGRAYGL-specific T cells from most EBV-seropositive individuals could also be detected in the peripheral blood of vaccine recipients. The vaccine was well tolerated, with the main side effect being mild to moderate injection site reactions. After a 2- to 12-year follow-up, 1/2 placebo vaccinees who acquired EBV developed infectious mononucleosis, whereas 4/4 vaccinees who acquired EBV after completing peptide vaccination seroconverted asymptomatically. Single-epitope vaccination did not predispose individuals to disease, nor did it significantly influence development of a normal repertoire of EBV-specific CD8(+) T-cell responses following seroconversion.