Table_1_Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries.docx

BackgroundImmunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination.
AimWe studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.
Materials and methodsFrom a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups.
ResultsGeometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year.
ConclusionsAn aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.

### 背景
无细胞百日咳（acellular pertussis, aP）疫苗的免疫原性传统上通过检测抗体应答进行评估，但疫苗接种后抗体浓度会快速衰减。然而，记忆B细胞对于维持长期保护至关重要，因此可能是评估疫苗接种后百日咳免疫力的重要指标。

### 研究目的
本研究针对芬兰、荷兰与英国三个国家的四个不同年龄组人群，探究无细胞百日咳加强疫苗诱导的百日咳特异性记忆B细胞（再）活化情况。

### 材料与方法
本研究数据来自一项IV期纵向干预研究，共纳入268名受试者，覆盖芬兰、荷兰及英国，所有受试者均接种三组分百日咳加强疫苗，按年龄分为四组：儿童组（7~10岁，n=53）、青少年组（11~15岁，n=66）、年轻成人组（20~34岁，n=74）以及老年组（60~70岁，n=75）。分别在基线、接种后第28天及接种后1年时，通过百日咳毒素（pertussis toxin, Ptx）、丝状血凝素（filamentous haemagglutinin, FHA）以及百日咳黏附素（pertactin, Prn）特异性酶联免疫斑点（ELISpot）试验检测记忆B细胞水平。既往检测获得的抗体结果可供对照分析。此外，本研究根据受试者基线记忆B细胞频率进行分组，并对各组的疫苗应答情况开展监测。

### 结果
百日咳抗原的基线记忆B细胞频率几何均数（geometric mean, GM）较低。接种后第28天，各年龄组的记忆B细胞频率均出现升高，且加强免疫后1年时仍高于基线水平。第28天时，青少年组的记忆B细胞频率最高（Ptx、FHA与Prn的几何均数分别为5、21和13），老年组最低（分别为2、9和3）。针对Prn的检测结果显示，第28天的记忆B细胞频率与第28天及1年时的抗体浓度呈中至强相关性。基线时记忆B细胞频率＞1/10万外周血单个核细胞（peripheral blood mononuclear cell, PBMC）的受试者，在接种后28天及1年时的记忆应答水平显著更高。

### 结论
无细胞百日咳加强疫苗可在所有年龄组中（再）活化记忆B细胞。接种后1年记忆B细胞频率仍维持升高，提示免疫记忆得到增强。但老年人群的抗原特异性记忆B细胞活化程度较弱，这可能与免疫衰老有关。此外，基线时循环记忆B细胞的存在对记忆B细胞应答具有正向影响。本研究已在www.clinicaltrialsregister.eu注册，注册号为2016-003678-42。