Holmlund Emma, Quiambao Beatriz, Ollgren Jukka, Jaakkola Teija, Neyt Cécile, Poolman Jan, Nohynek Hanna, Käyhty Helena
National Institute for Health and Welfare, Department of Vaccination and Immune Protection, PL 30, 00271 Helsinki, Finland.
Clin Vaccine Immunol. 2009 Jun;16(6):916-23. doi: 10.1128/CVI.00050-09. Epub 2009 Apr 29.
This study focuses on the immunogenicity of the following three pneumococcal vaccine candidate proteins in Filipino infants, all inducing protection in animal models: pneumococcal histidine triad protein D (PhtD), choline binding protein A (CbpA), and the lysozyme LytC. The immunoglobulin G antibody concentrations to PhtD, its putative, protective, and exposed C-terminal fragment (PhtD C), CbpA, and LytC were measured by enzyme immunoassay in 52 serum samples from pregnant women, 39 cord blood samples, and consecutive serum samples (n = 263) from 52 newborns between 6 weeks and 10 months of age scheduled to be taken at six time points. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel to the serum samples. The antibody concentrations in the cord blood samples were similar to those in the samples from the mothers. In infant sera, the geometric mean antibody concentrations (GMCs) for all three proteins decreased until the age of 18 weeks and started to increase after that age, suggesting that the infants' own antibody production started close to the age of 4 to 5 months. The increase in GMCs by age, most clear-cut for CbpA, was associated with pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C concentrations but correlated well (r of 0.89 at 10.5 months), suggesting that antibodies are directed to the supposedly exposed and protective C-terminal part of PhtD. Our results show that young children are able to develop an antibody response to PhtD, CbpA, and LytC and encourage the development of pneumococcal protein vaccines for this age group.
本研究聚焦于以下三种肺炎球菌候选疫苗蛋白在菲律宾婴儿中的免疫原性,这三种蛋白在动物模型中均能诱导产生保护作用:肺炎球菌组氨酸三联体蛋白D(PhtD)、胆碱结合蛋白A(CbpA)和溶菌酶LytC。通过酶免疫测定法,检测了52份孕妇血清样本、39份脐带血样本以及52名6周龄至10月龄新生儿在六个时间点采集的连续血清样本(n = 263)中针对PhtD、其假定的、具有保护作用的、暴露的C末端片段(PhtD C)、CbpA和LytC的免疫球蛋白G抗体浓度。在采集血清样本的同时,采集鼻咽拭子以检测肺炎球菌携带情况。脐带血样本中的抗体浓度与母亲样本中的相似。在婴儿血清中,所有三种蛋白的几何平均抗体浓度(GMCs)在18周龄前下降,之后开始上升,这表明婴儿自身的抗体产生在接近4至5月龄时开始。GMCs随年龄增加,CbpA最为明显,这与肺炎球菌携带情况相关。抗PhtD浓度高于抗PhtD C浓度,但相关性良好(10.5月龄时r为0.89),表明抗体针对的是PhtD假定的暴露且具有保护作用的C末端部分。我们的结果表明,幼儿能够对PhtD、CbpA和LytC产生抗体反应,并鼓励为该年龄组开发肺炎球菌蛋白疫苗。