在12、18或24个月时用4CMenB加强免疫后杀菌抗体的持久性以及4岁时接种第五剂的免疫原性——一项随机对照试验的3期扩展研究
Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24months and immunogenicity of a fifth dose administered at 4years of age-a phase 3 extension to a randomised controlled trial.
作者信息
Iro Mildred A, Snape Matthew D, Voysey Merryn, Jawad Sena, Finn Adam, Heath Paul T, Bona Gianni, Esposito Susanna, Diez-Domingo Javier, Prymula Roman, Odueyungbo Adefowope, Toneatto Daniela, Dull Peter, Pollard Andrew J
机构信息
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
出版信息
Vaccine. 2017 Jan 5;35(2):395-402. doi: 10.1016/j.vaccine.2016.11.009. Epub 2016 Nov 30.
BACKGROUND
4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age.
METHODS
A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6month schedule.
RESULTS
At baseline (prior to vaccination), the proportion of participants (n=468) with hSBA titers⩾5 was similar across all followon groups: 89-100% against 5/99; 12-35% for H44/76; 8-12% for NZ98/254 and 53-80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n=206). Following a dose of 4CMenB at 4years of age, this increased to 100% (5/99), 97-100% (H44/76), 80-95 % (NZ98/254) and 84-100% (M10713) (n=210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n=192).
CONCLUSION
Waning of protective antibodies occurred 24–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.
背景
4CMenB疫苗在婴幼儿中具有免疫原性。我们评估了在12、18或24月龄接种第四剂疫苗后人补体血清杀菌活性（hSBA）的持久性，并对4岁时接种第五剂疫苗后的抗体反应进行了特征分析。
方法
这是一项在四个国家（中心数量）开展的3期开放标签、多中心扩展研究，该研究是一项随机对照试验的扩展：捷克共和国（19个）、意大利（4个）、西班牙（4个）和英国（4个）。招募了未接种过4CMenB疫苗或之前在婴幼儿期接受过多种3剂基础免疫接种方案及一剂加强疫苗（后续组）的4岁儿童。采集静脉血样本以测定针对四种参考菌株的hSBA；这些参考菌株作为评估对每种疫苗抗原（NadA（5/99）、fHbp（H44/76）、PorA（NZ98/254）和NHBA（M10713））免疫的靶点，在基线时（所有参与者接种疫苗前）以及所有未接种疫苗和后续组中按2、3、4程序进行基础免疫的参与者以及三分之一按2、4、6月龄程序进行基础免疫的后续组参与者接种一剂4CMenB疫苗后1个月采集样本。
结果
在基线时（接种疫苗前），所有后续组中hSBA滴度≥5的参与者比例（n = 468）相似：针对5/99为89 - 100%；针对H44/76为12 - 35%；针对NZ98/254为8 - 12%；针对M10713为53 - 80%，而未接种疫苗的对照组（n = 206）分别为5%、0%、0%和60%。在4岁时接种一剂4CMenB疫苗后，这一比例分别增至100%（5/99）、97 - 100%（H44/76）、80 - 95%（NZ98/254）和84 - 100%（M10713）（n = 210），而未接种疫苗的对照组（n = 192）分别为89%、70%、24%和76%。
结论
无论加强免疫时的年龄如何，在婴幼儿加强免疫后24 - 36个月保护性抗体出现下降。针对目标菌株5/99和M10713这种情况最不明显。在4岁时接种加强疫苗后出现了强烈的记忆反应。
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