Hodgson Abraham, Forgor Abudulai Adams, Chandramohan Daniel, Reed Zarifah, Binka Fred, Bevilacqua Cornelia, Boutriau Dominique, Greenwood Brian
Navrongo Health Research Centre, Ministry of Health, Navrongo, Ghana.
PLoS One. 2008 May 14;3(5):e2159. doi: 10.1371/journal.pone.0002159.
Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana.
In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres > or = 1:8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres > or = 1:8 or SBA-MenC titres > or = 1:8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 microg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 microg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6-28.1] of doses vs 14.1%; 95% CI [10.9-17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study.
Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt.
Controlled-Trials.com ISRCTN35754083.
在婴儿期将脑膜炎球菌疫苗与常规免疫接种相结合，可能会减轻脑膜炎球菌性脑膜炎的负担，尤其是在非洲的脑膜炎带地区。我们评估了在加纳北部给婴儿接种的一种研究性白百破-乙肝/ Hib-AC结合疫苗的免疫原性、免疫反应的持久性、免疫记忆和安全性。
在这项II期双盲、随机对照研究中，280名婴儿在6、10和14周龄时分别用白百破-乙肝/ Hib-AC或白百破-乙肝/ Hib疫苗进行基础免疫。在12月龄时，每组儿童接受一剂A+C群多糖激发剂量。在基础免疫程序的第3剂接种前、接种后1个月以及激发剂量接种前和接种后1个月评估抗体反应。第3剂接种后1个月，研究组中分别有87.8%和88.2%的受试者抗A群脑膜炎球菌杀菌抗体（SBA-MenA）和抗C群脑膜炎球菌杀菌抗体（SBA-MenC）滴度≥1:8。研究组儿童对常规扩大免疫规划（EPI）程序中接种的5种抗原的血清保护/血清阳性率不低于对照组。在激发前12月龄时，研究组中SBA-MenA滴度≥1:8或SBA-MenC滴度≥1:8的受试者百分比显著高于对照组（分别为47.7%对25.7%和56.4%对5.1%）。在白百破-乙肝/ Hib-AC组中，接种10μg A群多糖后SBA-MenA几何平均滴度（GMT）升高了14.0倍，而对照组升高了3.8倍。用10μg C群多糖激发后，SBA-MenC滴度相应的升高倍数分别为18.8和1.9。两组在基础免疫接种或激发剂量接种后的反应原性相似，但基础免疫接种后肿胀（3级）在疫苗组儿童中比对照组更常见（分别为23.7%；95%CI[19.6 - 28.1]剂次对14.1%；95%CI[10.9 - 17.8]剂次）。在整个研究期间共报告了59例严重不良事件（包括8例死亡），均与疫苗接种无关。
对于常规EPI程序中使用的5种常见抗原，白百破-乙肝/ Hib-AC三剂基础免疫接种不劣于白百破-乙肝/ Hib，并且在大多数婴儿中诱导了针对A群和C群脑膜炎奈瑟菌的杀菌抗体。到12月龄时，近一半婴儿的A群和C群杀菌抗体水平已降至与保护相关的滴度以下，这证实大约在该年龄需要一剂加强剂量。多糖激发后显示出增强的记忆反应。这种疫苗可以预防7种重要的儿童疾病（包括A群和C群脑膜炎球菌），在非洲脑膜炎带国家具有特别的价值。
Controlled-Trials.com ISRCTN35754083。
