National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, Netherlands.
Institute of Biomedicine, Microbiology, Virology and Immunology, and Turku University Hospital, University of Turku, Turku, Finland.
Front Immunol. 2022 May 23;13:864674. doi: 10.3389/fimmu.2022.864674. eCollection 2022.
Immunogenicity 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.
We studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.
From 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.
Geometric 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.
An 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.
无细胞百日咳（aP）疫苗的免疫原性通常通过测量抗体反应来评估，但接种疫苗后抗体浓度会迅速下降。然而，记忆 B 细胞在维持长期保护方面至关重要，因此在评估接种疫苗后百日咳免疫力时可能是一个重要因素。
我们研究了在芬兰、荷兰和英国的四个不同年龄组中，aP 加强疫苗接种引起的百日咳特异性记忆 B 细胞（再）激活。
来自一项四期纵向干预研究，共有 268 名参与者（芬兰 n=53 名，荷兰 n=66 名，英国 n=74 名，年龄 7-10 岁；芬兰 n=75 名，荷兰 n=66 名，英国 n=74 名，年龄 11-15 岁；芬兰 n=75 名，荷兰 n=66 名，英国 n=74 名，年龄 20-34 岁；芬兰 n=75 名，荷兰 n=66 名，英国 n=74 名，年龄 60-70 岁）接受了三组分百日咳加强疫苗：儿童（7-10 岁，n=53）、青少年（11-15 岁，n=66）、年轻成人（20-34 岁，n=74）和老年人（60-70 岁，n=75）。在接种疫苗前、第 28 天和 1 年后通过百日咳毒素（Ptx）、丝状血凝素（FHA）和 pertactin（Prn）特异性 ELISpot 测定法测量记忆 B 细胞。以前测量的抗体结果可用于比较。此外，根据基线记忆 B 细胞频率将研究参与者分为不同的组，监测疫苗接种后的反应。
在基线时，针对百日咳抗原的记忆 B 细胞频率的几何均数（GM）较低。在接种疫苗后 28 天内，每个年龄组的这些频率都有所增加，并且在加强疫苗接种后 1 年仍高于基线。在青少年中观察到最高的频率（GM：分别为 5、21 和 13，针对 Ptx、FHA 和 Prn），在老年人中观察到最低的频率（GM：分别为 2、9 和 3）。在第 28 天和第 1 年观察到 Prn 抗体浓度与记忆 B 细胞频率之间存在中度至强相关性。基线时记忆 B 细胞频率>1/100,000 PBMC 与第 28 天和 1 年后的记忆反应显著相关。
aP 加强疫苗在所有年龄组中（重新）激活了记忆 B 细胞。一年后仍然升高的记忆 B 细胞频率表明增强了免疫记忆。然而，老年组记忆 B 细胞的抗原特异性激活似乎较弱，这可能反映了免疫衰老。此外，基线时存在循环记忆 B 细胞会对记忆 B 细胞反应产生积极影响。本研究在 www.clinicaltrialsregister.eu 上注册：编号 2016-003678-42。
