Vaccine. 2018 Sep 11;36(38):5781-5788. doi: 10.1016/j.vaccine.2018.07.076. Epub 2018 Aug 10.
The potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation.
In this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMR-RIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and anti-mumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT).
Each formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (-10.94%) was beyond the pre-defined limit of -10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles.
One dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a non-inferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-year-old children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.
活病毒疫苗的效力会随时间推移而降低。我们比较了两种不同效力的 GSK 麻疹-腮腺炎-风疹疫苗（MMR-RIT）制剂与市售 MMR II 制剂的免疫原性和安全性。
在这项 III 期观察者盲法临床研究（NCT01681992）中，4516 名 12-15 月龄健康儿童以 1:1:1 的比例随机分配，接受一剂本研究最低效力的 MMR-RIT（MMR-RIT-Min）或本研究第二低效力的 MMR-RIT（MMR-RIT-Med），或对照 MMR II 疫苗。第一剂后 42 天接种第二剂（MMR-RIT 或 MMR II）。该研究有 10 个主要共同目标，通过分层程序评估 MMR-RIT 与 MMR II 的免疫原性。通过 ELISA 测量抗麻疹和抗风疹抗体，通过 ELISA 和未经增强的蚀斑减少中和试验（PRNT）测量抗腮腺炎抗体。
每种制剂在每剂 MMR 后都能诱导针对所有疫苗抗原的免疫应答。虽然 MMR-RIT-Min 的主要目标没有达到，但 MMR-RIT-Med 诱导的免疫应答通过 ELISA 测量针对三种疫苗抗原符合预先指定的非劣效性标准。通过 PRNT 测量的 MMR-RIT-Med 针对腮腺炎的免疫应答未能达到血清反应率的非劣效性标准：97.5%置信区间下限（-10.94%）超出了预先定义的-10%界限。第 2 剂后，各组的免疫应答无差异。未发现安全性问题，MMR-RIT 和 MMR II 疫苗具有相似的反应原性和安全性。
与商业 MMR II 疫苗相比，一剂效力较低的 MMR-RIT 制剂（MMR-RIT-Med）在一岁儿童中通过 ELISA 测量诱导了非劣效的免疫应答。尽管差异具有不确定的临床相关性，但通过未经增强的 PRNT 测量针对腮腺炎病毒的免疫应答未能显示非劣效性。接种第二剂后，MMR-RIT 和 MMR II 组之间的免疫应答相似。
