在阿根廷一岁儿童中进行的麻疹、腮腺炎和风疹（MMR）和黄热病疫苗联合接种的免疫反应：一项随机非劣效性试验。
Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.
机构信息
Dirección de Control de Enfermedades Inmunoprevenibles, Ministerio de Salud de Argentina, Buenos Aires, Argentina.
Global Immunization Division, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
出版信息
BMC Infect Dis. 2023 Mar 17;23(1):165. doi: 10.1186/s12879-023-08114-1.
BACKGROUND
In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration.
METHODS
We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMRYF), MMR followed by YF vaccine four weeks later (MMRYF), or YF followed by MMR vaccine four weeks later (YFMMR). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests.
RESULTS
Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMRYF group versus 96.3% in the MMRYF group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMRYF versus 94.7% MMRYF, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMRYF versus 97.9% MMRYF, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMRYF versus 97.5% YFMMR, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted.
CONCLUSION
Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration.
TRIAL REGISTRATION
The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.
背景
在黄热病（YF）流行地区，麻疹、腮腺炎和风疹（MMR）和 YF 疫苗通常在儿童免疫接种计划中同时接种。由于这些是活疫苗，我们评估了潜在的免疫干扰，这可能会导致同时接种。
方法
我们在阿根廷米西奥内斯省进行了一项针对 1 岁健康儿童的开放性、随机非劣效性试验。儿童随机分为三组（1:1:1）：MMR 和 YF 疫苗同时接种（MMRYF）、MMR 疫苗接种后 4 周接种 YF 疫苗（MMRYF）或 YF 疫苗接种后 4 周接种 MMR 疫苗（YFMMR）。接种前和接种后 28 天采集血样，检测麻疹、腮腺炎和风疹的免疫球蛋白 G 抗体和 YF 病毒特异性中和抗体。使用 -5%非劣效性边界评估血清转化率的非劣效性。采用 Kruskal-Wallis 检验比较抗体浓度。
结果
在 851 名随机儿童中，738 名儿童正确接种疫苗，有≥1 次随访样本，且纳入意向治疗人群。所有抗原的血清转化率均观察到非劣效性（麻疹血清转化率：MMRYF 组为 97.9%，MMRYF 组为 96.3%，差异为 1.6%[90%CI-1.5，4.7]；风疹：MMRYF 组为 97.9%，MMRYF 组为 94.7%，差异为 3.3%[-0.1，6.7]；腮腺炎：MMRYF 组为 96.7%，MMRYF 组为 97.9%，差异为-1.3%[-4.1，1.5]；YF：MMRYF 组为 96.3%，YFMMR 组为 97.5%，差异为-1.2%[-4.2，1.7]）。同时接种后，风疹抗体浓度和 YF 滴度显著降低；麻疹和腮腺炎浓度不受影响。
结论
虽然两种抗原的抗体水平较低，但仍实现了有效的血清转化率，且不受同时接种的影响。需要权衡较低的抗体水平的影响与错过接种疫苗的机会，以确定 MMR 和 YF 疫苗接种的最佳时间。
试验注册
该研究于 2017 年 11 月 12 日在 ClinicalTrials.gov（NCT03368495）进行了回顾性注册。
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