van Ravenhorst Mariëtte B, van der Klis Fiona R M, van Rooijen Debbie M, Knol Mirjam J, Stoof Susanne P, Sanders Elisabeth A M, Berbers Guy A M
Centre for Infectious Disease Control (Cib), National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
Centre for Infectious Disease Control (Cib), National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Vaccine. 2017 Aug 24;35(36):4745-4752. doi: 10.1016/j.vaccine.2017.06.053. Epub 2017 Jun 28.
Adolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster.
Healthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year.
Of 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds.
Both MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term.
青少年被认为是人群中脑膜炎球菌的主要传播者。幼儿接种C群脑膜炎球菌（MenC）结合疫苗后，MenC抗体水平迅速下降，导致青少年抗体水平较低。在本研究中，我们比较了青少年接种破伤风类毒素结合MenC（MenC-TT）或A、C、W、Y群脑膜炎球菌（MenACWY-TT）疫苗加强免疫后的MenC免疫反应，旨在确定最佳加强免疫年龄。
在幼儿期接受过单剂MenC-TT疫苗的健康10岁、12岁和15岁儿童被随机分配接受MenC-TT或MenACWY-TT疫苗。在加强免疫前、后1个月和1年后测定MenC血清杀菌抗体（rSBA）滴度、MenC多糖（PS）特异性IgG、IgG1和IgG2以及MenC特异性IgG和IgA记忆B细胞。通过比较加强免疫1年后疫苗接种者之间的几何平均滴度（GMT）来检验非劣效性。
501名参与者中，464名（92.6%）纳入“符合方案”队列分析。加强免疫1个月后，所有参与者的MenC rSBA滴度均升高（所有组均>24,000），MenC-PS特异性IgG水平升高。加强免疫1年后，单价疫苗接种者的MenC GMT较高，未显示出非劣效性，但462/464名（99.6%）参与者的MenC rSBA滴度维持在保护性水平。IgG水平主要由IgG1组成，但IgG1和IgG2的升高水平相似。两种疫苗均使循环中MenC-PS特异性IgG和IgA记忆B细胞数量明显增加。在1个月至1年期间，10岁儿童的抗体衰减率最高。
加强免疫后，MenC-TT和MenACWY-TT疫苗均诱导了强大的保护性MenC免疫反应，尽管1年后MenACWY-TT疫苗未显示出非劣效性。我们的结果强调了脑膜炎球菌加强免疫最佳时机对于长期预防MenC疾病的重要性。
