Martinón-Torres Federico, Simko Robert, Ebert Rolf, Rämet Mika, Zocchetti Céline, Syrkina Olga, Bchir Siham, Bertrand-Gerentes Isabelle
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago (SERGAS) and Universitario de Santiago de Compostela, Santiago de Compostela, Galicia, Spain.
Genetics, Vaccines, Infections and Pediatrics Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain.
Infect Dis Ther. 2025 May;14(5):991-1010. doi: 10.1007/s40121-025-01121-6. Epub 2025 Apr 1.
Many countries recommend vaccination against Neisseria meningitidis serogroups A, C, W, and Y in infants and young children to prevent invasive meningococcal disease. We evaluated the immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) booster in children primed with the same meningococcal vaccine 5 years earlier. Immune persistence following priming vaccination was also evaluated, and the study is ongoing to generate 10 years' post-priming data.
Healthy children, vaccinated with MenACYW-TT 5 years earlier as toddlers, were enrolled. Participants were randomized to receive MenACYW-TT booster (group 1) or no booster (group 2), stratified by country and meningococcal serogroup C (MenC) vaccination status (primed at age ≤ 1 year vs. naive). Antibodies against each serogroup were measured by serum bactericidal assay using human complement (hSBA). Seroresponse sufficiency at 30 days post-booster was demonstrated if the lower limit of the one-sided 97.5% confidence interval (CI) of the seroresponse rate (proportion of participants with post-vaccination titers ≥ 1:16 when baseline titers were < 1:8 or with a ≥ fourfold increase when baseline titers were ≥ 1:8) was > 75% for each serogroup. Seroprotection rates (proportion with hSBA titers ≥ 1:8) and geometric mean titers (GMTs) for each serogroup were also assessed.
A total of 209 participants were enrolled across 26 sites in Finland, Germany, Hungary, and Spain (group 1, n = 93; group 2, n = 116). Five years post-priming, GMTs, and seroprotection rates were higher than those observed before priming vaccination in both groups, indicating long-term persistence. Booster seroresponse rates in group 1 for all serogroups ranged from 93.2% to 98.9%, with seroresponse sufficiency demonstrated (lower limit of one-sided 97.5% CIs for the seroresponse rates ranging from 85.7% to 93.8%). Seroprotection rates and GMTs post-booster increased across all serogroups, with nearly all participants seroprotected, suggesting adequate booster response. Seroresponse was comparable between MenC-primed and MenC-naive participants. No new safety concerns were identified.
MenACYW-TT provides long-term immune persistence and a robust immune response when administered as a booster in children primed 5 years earlier.
Clinicaltrials.gov, NCT04936685; EudraCT: 2021-000104-38; WHO: U1111-1255-4941. Graphical abstract available for this article.
许多国家建议对婴幼儿接种A、C、W和Y血清群的脑膜炎奈瑟菌疫苗，以预防侵袭性脑膜炎球菌病。我们评估了一种四价脑膜炎球菌破伤风类毒素结合疫苗（MenACYW-TT）加强针在5年前接种过相同脑膜炎球菌疫苗的儿童中的免疫原性和安全性。还评估了初次接种疫苗后的免疫持久性，该研究正在进行以获取初次接种后10年的数据。
纳入5年前幼儿期接种过MenACYW-TT的健康儿童。参与者被随机分为接受MenACYW-TT加强针（第1组）或不接受加强针（第2组），按国家和脑膜炎球菌C血清群（MenC）接种状态（1岁及以下时接种过与未接种过）分层。使用人补体通过血清杀菌试验（hSBA）检测针对各血清群的抗体。如果血清反应率（基线滴度<1:8时接种后滴度≥1:16或基线滴度≥1:8时增加≥4倍的参与者比例）的单侧97.5%置信区间（CI）下限对于每个血清群>75%，则证明加强针接种后30天血清反应充足。还评估了每个血清群的血清保护率（hSBA滴度≥1:8的比例）和几何平均滴度（GMT）。
芬兰、德国、匈牙利和西班牙的26个地点共纳入209名参与者（第1组，n = 93；第2组，n = 116）。初次接种后5年，两组的GMT和血清保护率均高于初次接种疫苗前观察到的水平，表明具有长期持久性。第1组中所有血清群的加强针血清反应率在93.2%至98.9%之间，证明血清反应充足（血清反应率的单侧97.5% CI下限在从至857%至93.8%之间）。加强针接种后的血清保护率和GMT在所有血清群中均有所增加，几乎所有参与者都获得了血清保护，表明加强针反应充分。MenC接种过与未接种过的参与者之间血清反应相当。未发现新的安全问题。
MenACYW-TT在5年前接种过的儿童中作为加强针接种时可提供长期免疫持久性和强大的免疫反应。
Clinicaltrials.gov，NCT04936685；EudraCT：2021-000104-38；WHO：U1111-1255-4941。本文有图形摘要。
