Findlow H, Plikaytis B D, Aase A, Bash M C, Chadha H, Elie C, Laher G, Martinez J, Herstad T, Newton E, Viviani S, Papaspyridis C, Kulkarni P, Wilding M, Preziosi M P, Marchetti E, Hassan-King M, La Force F M, Carlone G, Borrow R
Vaccine Evaluation Unit, Health Protection Agency North West, Clinical Sciences Building, Manchester Royal Infirmary, Manchester, UK.
Clin Vaccine Immunol. 2009 Jul;16(7):969-77. doi: 10.1128/CVI.00068-09. Epub 2009 May 27.
A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a > or = 4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group.
先前进行了一项双盲、随机、对照的I期研究，以评估一种新型A群结合疫苗（PsA-TT）在18至35岁志愿者中的安全性、免疫原性和抗体持久性。受试者分别接受一剂PsA-TT结合疫苗、A/C群脑膜炎球菌多糖疫苗（PsA/C）或破伤风类毒素疫苗。通过标准化的A群特异性免疫球蛋白G（IgG）酶联免疫吸附测定（ELISA）以及使用兔补体的血清杀菌抗体（SBA）测定（rSBA），证明结合疫苗是安全且具有免疫原性的。本报告详细介绍了使用另外四种免疫测定方法对血清进行的进一步分析，以研究不同免疫测定之间的关系。所使用的免疫测定方法包括使用人补体的SBA测定（hSBA）、A群特异性IgG多重微珠测定以及使用两种不同方法的两种吞噬调理抗体（OPA）测定。对于每个疫苗组，在接种疫苗前以及接种后4周、24周和48周，对所有测定方法确定几何平均浓度或几何平均滴度。使用Pearson相关系数，利用所有可用访视的数据评估六种测定方法之间的关系。通过ELISA获得的A群特异性IgG浓度与通过多重微珠测定获得的浓度之间观察到极佳的相关性。hSBA和rSBA滴度呈中度相关，尽管具有推定保护性滴度的受试者比例以及显示升高≥4倍的受试者比例相似。两种OPA方法相关性较弱，并且与其他免疫测定仅具有低相关性。PsA-TT组中hSBA与A群特异性IgG之间的相关性高于PsA/C组。
