Kelly Dominic F, Snape Matthew D, Perrett Kirsten P, Clutterbuck Elizabeth A, Lewis Susan, Blanchard Rohner Geraldine, Jones Meryl, Yu Ly-Mee, Pollard Andrew J
Oxford Vaccine Group, Department of Paediatrics, Oxford University, Oxford, UK.
Immunology. 2009 May;127(1):134-43. doi: 10.1111/j.1365-2567.2008.02934.x.
The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity.
诱导产生针对病原体的持续保护性抗体水平是儿童感染性疾病免疫接种的一个重要目标。然而，与生命后期相比，婴儿期免疫接种后抗体持久性较差。C群脑膜炎球菌（MenC）是儿童菌血症和脑膜炎的一个重要病因。使用针对MenC的蛋白-多糖结合疫苗与侵袭性疾病发病率的显著下降相关。然而，在婴儿期进行三剂基础免疫接种后1年多，疫苗效力可忽略不计，且这与初次免疫反应后抗体的快速下降相一致。该年龄组中产生持续性抗体的细胞机制尚不清楚。在对外周血B细胞进行更大规模研究之前，一个重要的前奏是了解免疫接种后的B细胞动力学。我们测量了在2、3和4月龄时接种CRM(197)（交叉反应物质；突变白喉类毒素）结合的MenC疫苗的婴儿中MenC特异性和白喉特异性浆细胞及记忆B细胞的动力学。与第三剂后浆细胞迅速出现相比，第一剂后浆细胞反应延迟更明显。第三剂后所有时间点均可检测到记忆B细胞，而第一剂后记忆B细胞频率较低。本研究提供了关于婴儿初次免疫接种程序后B细胞动力学的数据，可为进一步研究体液免疫的潜在细胞机制提供依据。
