Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre and Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Pediatr Infect Dis J. 2012 Oct;31(10):1069-73. doi: 10.1097/INF.0b013e318262528c.
Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 3½ years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 3½ years of age.
Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit.
Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55- .73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1 - 10.9) compared with 7.2 EL.U/mL (3.9 - 13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2).
Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood.
在婴儿期接受过 Hib-MenC-TT（结合型 Hib-MenC 疫苗）和白喉、破伤风、无细胞百日咳、灭活脊髓灰质炎疫苗（DTaP-IPV）免疫接种的儿童，在 12 个月大时再接受 12 个月的 Hib-MenC-TT 加强剂量后，针对乙型流感嗜血杆菌（Hib）和脑膜炎奈瑟球菌 C 群（MenC）的抗体在 3 岁半后仍能更好地持续存在，而在那些接受单价 MenC-CRM197 和 DTaP-IPV-Hib（也为 TT 结合型）的儿童中则不然。在接受 DTaP-IPV 免疫接种的儿童中，5 个月和 12 个月时针对丝状血凝素和 pertactin 的百日咳抗体滴度高于接受 DTaP-IPV-Hib 免疫接种的儿童。我们评估了在 3 岁半时接受学前 DTaP-IPV 加强剂量后，这些差异是否持续到儿童后期。
英国和波兰的儿童先前参加了上述随机对照试验，在 5 岁时采集了血样。比较了在 2、3 和 4 个月时接受 DTaP-IPV/Hib-MenC-TT（Hib-MenC-TT 组）和接受单价 MenC-CRM197 和 DTaP-IPV-Hib（对照组）的儿童的抗多聚核糖醇核糖醇磷酸（Hib）IgG 和脑膜炎球菌杀菌抗体（兔补体）滴度。在本次就诊时还测量了针对丝状血凝素、pertactin 和 pertussis 毒素的抗体浓度。
共有 268 名年龄在 58-64 个月的参与者被纳入。Hib-MenC-TT 组 194 名参与者中有 115 名（59.3%[52.0-66.3%]）和对照组 58 名参与者中有 26 名（44.8%[31.7-58.5%]）的 MenC 兔补体滴度≥1:8。Hib-MenC-TT 组和对照组的 MenC 兔补体几何平均滴度分别为 30.4 和 11.3，比值为 2.70（1.55-0.73）。抗多聚核糖醇核糖醇磷酸（Hib）IgG 浓度≥1.0μg/mL 的 Hib-MenC-TT 组 197 名参与者中有 171 名（86.8%[81.3-91.2%]）和对照组 58 名参与者中有 36 名（62.1%[48.4-74.5%]）。Hib-MenC-TT 组和对照组的抗多聚核糖醇核糖醇磷酸 IgG 几何平均浓度（GMC）分别为 3.82 和 1.67，比值为 2.29（1.59-3.28）。68 名英国 58-63 岁的参与者进行了 pertussis 抗原分析（44 名接受 DTaP-IPV 接种者，14 名接受 DTaP-IPV-Hib 接种者）。接受 DTaP-IPV 和 DTaP-IPV-Hib 免疫接种的参与者的抗 pertussis 毒素 IgG GMC 相似：8.2 EL.U/mL（6.1-10.9）与 7.2 EL.U/mL（3.9-13.4）。接受 DTaP-IPV 接种者的抗丝状血凝素 IgG GMC 较高（164.7 EL.U/mL[119.4-227.1]），而接受 DTaP-IPV-Hib 接种者的抗丝状血凝素 IgG GMC 较低（66.8 EL.U/mL[43.8-101.7]），抗 pertactin IgG GMC 也较高：102.8 EL.U/mL（67.1-157.3）与 23.4 EL.U/mL（15.1-36.2）。
用于 Hib 和 MenC 婴儿免疫接种的疫苗在增强 Hib-MenC-TT 加强剂量的反应能力方面存在差异，这种差异至少持续到 5 岁。学前接受 DTaP-IPV 加强剂量后，抗 pertussis 抗体的持续存在也受到 2、3 和 4 个月时接受免疫接种的影响，突出了婴儿免疫接种在维持儿童期抗体水平方面的重要性。
