近日，美国马里兰大学医学院教授Wilbur H Chen及其课题组报道了在马里9个月和15个月时与常规儿童疫苗联合接种针对a、C、W、Y和X血清群的五价脑膜炎球菌结合疫苗的安全性和免疫原性。这一研究成果发表在2025年3月11日出版的国际学术期刊《柳叶刀》上。

背景:侵袭性脑膜炎球菌病是非洲脑膜炎带的一个破坏性公共卫生问题。课题组人员评估了针对血清群a、C、Y、W和X （NmCV-5）的五价脑膜炎球菌结合疫苗（MenACWY-TT）与9月龄和15月龄的常规儿童疫苗联合使用时的安全性和免疫原性，相对于已获许可的四价脑膜炎球菌结合疫苗（MenACWY-TT）。

方法:在这项单中心、双盲、随机、对照、3期非劣效性试验中，在马里巴马科的疫苗接种中心招募了9-11个月大、已完成当地婴儿扩大免疫规划（EPI）疫苗接种的儿童。参与者在9个月的EPI访问时随机分配（1:1·2），在9个月或15个月的EPI访问时接受脑膜炎球菌疫苗接种。在每个参与者指定的EPI访问中，他们被随机分配第二次（2:1）接受NmCV-5或MenACWY-TT。研究疫苗和指定的扩大免疫疫苗由指定的未戴面具的研究人员制备和施用。父母或监护人、调查人员和所有其他试验工作人员对脑膜炎球菌疫苗分配不知情。脑膜炎球菌疫苗在9个月大时与麻疹和风疹疫苗（第一剂）和黄热病疫苗联合接种，或在15个月大时与麻疹和风疹疫苗（第二剂）联合接种。主要终点，血清保护反应，被定义为兔补体血清杀菌抗体滴度为8或更高，其估计值是在接种疫苗后28天显示这种反应的五种脑膜炎球菌血清组的参与者比例的差异，在按方案人群中进行评估。在两个年龄组的所有5个血清组中，预先指定的非劣效性裕度为-10%。与A、C、W或Y血清组中最低的MenACWY-TT血清保护反应相比，评估了NmCV-5血清保护反应对X血清组的非劣效性。安全性是次要终点，在经过修改的意向治疗人群中进行了为期6个月的评估，其中包括所有接受随机分配的脑膜炎球菌疫苗的参与者。

发现:在2022年3月24日至8月15日期间，1325名参与者被招募，并随机分配在9个月大（n=602）或15个月大（n=723）时接种脑膜炎球菌疫苗。在同一时期，分配到9个月疫苗接种组的602名参与者中有600人接种了脑膜炎球菌疫苗。在2022年9月27日至2023年2月6日期间，600名参与者在为期15个月的随访中接种了脑膜炎球菌疫苗。在两组中，400名参与者接受NmCV-5治疗，200名参与者接受MenACWY-TT治疗。在非劣效性分析中评估的每个方案人群包括564名在9个月时接种疫苗的参与者（373名接种了NmCV-5, 191名接种了MenACWY-TT）和549名在15个月时接种疫苗的参与者（367名接种了NmCV-5, 182名接种了MenACWY-TT）。在9月龄时接受NmCV-5治疗的按方案人群中，相对于MenACWY-TT，血清A组NmCV-5的血清保护患病率差异为0·0% (95% CI为-1·0至2·0)，血清C组为-0·5% (95% CI为-2·3至1·9)，血清W组为-3·0% (95% CI为-6·3至0·8)，血清Y组为-3·0% （95% CI为-5·4至0·4）。对于X血清组，在接受MenACWY-TT治疗的参与者中，相对于W血清组的血清保护，评估了非劣效性，差异为2.3% （95% CI 0.3至4.7）。15个月时接受NmCV-5治疗的受试者与15个月时接受MenACWY-TT治疗的受试者的血清保护率差异，A组为0.8% (95% CI为- 0.6 ~ 3.7)，C组为- 0.8% (95% CI为- 0.3 ~ 2.5)，W组为0.3% (95% CI为- 0.8 ~ 3.5)，Y组为1.4% （95% CI为- 0.6 ~ 4.8）。对于X血清组，在接受MenACWY-TT治疗的参与者中，对Y血清组的血清保护进行了非劣效性评估，差异为1.9% （95% CI 0·0至4·4）。在所有五个血清组中，两个年龄组的NmCV-5应答均不逊于MenACWY-TT应答。记录了6起严重不良事件，但没有一起被认为与疫苗接种有关。

研究结果表明，与一种获得许可的四价脑膜炎球菌结合疫苗相比，并与其他常规疫苗一起接种，单剂量NmCV-5是安全的，并在9个月的婴儿和15个月的幼儿中引发了非低免疫应答。

附：英文原文

Title: Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, W, Y, and X when co-administered with routine childhood vaccines at ages 9 months and 15 months in Mali: a single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial

Author: Fatoumata Diallo, Fadima C Haidara, Milagritos D Tapia, Clara P Dominguez Islas, Mark R Alderson, William P Hausdorff, Lionel Martellet, Nancy Hosken, Dhananjay Kapse, Prasad S Kulkarni, Kelly Townsend-Payne, Francesca Vanni, Christine M Posavad, Samba O Sow, Karen L Kotloff, Wilbur H Chen, Fatoumata Diallo, Fadima C. Haidara, Milagritos D. Tapia, Souleymane Diakité, Youssouf Traoré, Awa Traoré, Mamoudou Kodio, Clara P. Dominguez Islas, Fleesie A. Hubbard, William P. Hausdorff, Lionel Martellet, Nancy Hosken, Mark R. Alderson, Dhananjay Kapse, Prasad S. Kulkarni, Kelly Townsend-Payne, Francesca Vanni, Monica M. Farley, Brett S. Hanscom, Clifton W. Kelly, Christine M. Posavad, Samba O. Sow, Karen L. Kotloff, Wilbur H. Chen

Issue&Volume: 2025-03-11

Abstract: Background

Invasive meningococcal disease is a devastating public health problem for the African meningitis belt. We assessed the safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W, and X (NmCV-5) relative to a licensed, quadrivalent meningococcal conjugate vaccine (MenACWY-TT) when co-administered with routine childhood vaccines at ages 9 months and 15 months.

Methods

In this single-centre, double-blind, randomised, controlled, phase 3, non-inferiority trial, children aged 9–11 months who had completed their local infant Expanded Program on Immunization (EPI) vaccines were recruited at the Centre pour le Développement des Vaccins in Bamako, Mali. Participants were randomly assigned (1:1·2) at their 9-month EPI visits to receive a meningococcal vaccine at either their 9-month or 15-month EPI vaccination visits. At each participant's designated EPI visit, they were randomly assigned a second time (2:1) to receive either NmCV-5 or MenACWY-TT. Study vaccines and designated EPI vaccines were prepared and administered by assigned unmasked study personnel. Parents or guardians, investigators, and all other trial staff were masked to meningococcal vaccine assignments. The meningococcal vaccines were co-administered with a measles and rubella vaccine (first dose) and a yellow fever vaccine at age 9 months or with a measles and rubella vaccine (second dose) at age 15 months. The primary endpoint, seroprotective response, was defined as a rabbit complement serum bactericidal antibody titre of 8 or higher, with the estimand, given as the difference in the proportions of participants for each of the five meningococcal serogroups who showed this response 28 days after vaccination, assessed in the per-protocol population. The prespecified non-inferiority margin was –10% for all five serogroups in both age groups. The non-inferiority of the NmCV-5 seroprotective response to serogroup X was evaluated in comparison with the lowest seroprotective response for MenACWY-TT among serogroups A, C, W, or Y. Safety was a secondary endpoint, assessed over 6 months in a modified intention-to-treat population that included all participants who received a randomly assigned meningococcal vaccine. This trial is registered with ClinicalTrials.gov, NCT05093829.

Findings

Between March 24 and Aug 15, 2022, 1325 participants were enrolled and randomly assigned to receive a meningococcal vaccine at either age 9 months (n=602) or age 15 months (n=723). Meningococcal vaccines were administered to 600 of the 602 participants assigned to the 9-month vaccination group during that same period. Between Sept 27, 2022, and Feb 6, 2023, 600 participants received meningococcal vaccines at their 15-month visits. In both groups, 400 participants received NmCV-5 and 200 participants received MenACWY-TT. The per-protocol population assessed in the non-inferiority analysis included 564 participants vaccinated at age 9 months (373 who received NmCV-5 and 191 who received MenACWY-TT) and 549 participants vaccinated at age 15 months (367 who received NmCV-5 and 182 who received MenACWY-TT). Among the participants in the per-protocol population who received NmCV-5 at age 9 months, the difference in seroprotection prevalence for NmCV-5 relative to MenACWY-TT was 0·0% (95% CI –1·0 to 2·0) for serogroup A, –0·5% (–2·3 to 1·9) for serogroup C, –3·0% (–6·3 to 0·8) for serogroup W, and –3·0% (–5·4 to –0·4) for serogroup Y. For serogroup X, non-inferiority was assessed relative to seroprotection for serogroup W in participants who received MenACWY-TT, with a difference of 2·3% (95% CI 0·3 to 4·7). The difference in the prevalence of seroprotection among the participants who received NmCV-5 at age 15 months relative to participants who received MenACWY-TT at age 15 months was 0·8% (95% CI –0·6 to 3·7) for serogroup A, –0·8% (–3·3 to 2·5) for serogroup C, 0·3% (–1·8 to 3·5) for serogroup W, and 1·4% (–0·6 to 4·8) for serogroup Y. For serogroup X, non-inferiority was assessed in relation to seroprotection for serogroup Y in participants who received MenACWY-TT, with a difference of 1·9% (95% CI 0·0 to 4·4). NmCV-5 responses in both age groups were non-inferior to MenACWY-TT responses for all five serogroups. Six serious adverse events were recorded but none were deemed related to vaccination.

Interpretation

When compared with a licensed, quadrivalent meningococcal conjugate vaccine, and given alongside other routine vaccines, a single dose of NmCV-5 was safe and elicited a non-inferior immune response in infants aged 9 months and young children aged 15 months.

DOI: 10.1016/S0140-6736(25)00046-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00046-7/abstract