Sayi Takudzwa S, Sharapov Umid M, Matson Zachary, Coughlin Melissa M, Crooke Stephen N, An Qian, Knapp Jennifer K, Aziz Asma Binte, Yunus Mohammad, Haque Warda, Rana Sohel, Khan Md Al Fazal, Alexander James P, Kretsinger Katrina, Rota Paul A, Zaman Khalequ, Anand Abhijeet
US Centers for Disease Control and Prevention, Atlanta, GA, USA.
Independent Consultant, Atlanta, GA, USA.
Lancet Child Adolesc Health. 2025 May;9(5):306-314. doi: 10.1016/S2352-4642(25)00090-2. Epub 2025 Mar 31.
The first dose of measles-rubella (MR) vaccine is routinely administered to infants aged 9 months as part of a standard two-dose schedule. However, during large measles outbreaks and in other settings of increased circulation or increased risk, WHO recommends administering a supplementary dose at age 6 months to protect young infants. We aimed to assess the immunogenicity and safety of a first dose of MR vaccine administered to infants aged 6 months and its effect on the immune response to the routine MR vaccine at age 9 months.
This open-label, randomised trial enrolled healthy infants aged 6 months in Matlab, Bangladesh, who had never received an MR vaccine dose and had no history of measles or rubella. Using a computer-generated block randomisation scheme, infants were randomly assigned (1:1) to receive either two doses of the MR vaccine, one at age 6 months and the second at age 9 months (two-dose group), or one dose at age 9 months (one-dose group). Baseline characteristics were recorded for all enrolled participants at age 6 months. Blood samples were drawn for antibody assays before each vaccination and at final follow up when infants were aged 11 months. The primary outcome was immunogenicity of a first MR vaccine in infants aged 6 months or 9 months and the immunogenicity of a second MR vaccine in infants aged 9 months who received their first MR vaccine at 6 months. Immunogenicity was measured as the proportion of infants who seroconverted in the 12 weeks after vaccination at age 6 months or the 8 weeks after vaccination at age 9 months. Seroconversion was defined as a 4-times increase in IgG concentrations relative to the pre-vaccination concentrations or achieving seroprotective antibody concentrations between study timepoints. The modified intention-to-treat analysis included all infants who received MR vaccines per group assignment and had antibody results at baseline, 9 months, and 11 months. All enrolled infants were included in the safety analysis of the immediate reactions (observed by study staff at the fixed-site clinic in the first 30 min after vaccination), adverse events within 48 h of vaccination among infants in the two-dose group receiving their first MR vaccine at age 6 months, and adverse events observed by study staff or parents at any time during the study. The trial is registered on ClinicalTrials.gov, NCT03071575, and is closed to enrolment.
Between March 9, 2017, and March 18, 2018, 620 infants were enrolled and randomly assigned to the two study groups (312 in the two-dose group and 308 in the one-dose group). Of the 301 infants vaccinated at 6 months, 282 seroconverted for measles (94%, 95% CI 90-96), and 283 seroconverted for rubella (94%, 91-96). By 11 months, after receiving a second dose at age 9 months, 297 (cumulative 99%, 95% CI 97-100) infants seroconverted for measles and 297 infants seroconverted for rubella (cumulative 99%, 96-100). Of the 292 infants vaccinated at 9 months only, 291 seroconverted for both antigens by age 11 months (100%, 95% CI 98-100). 123 adverse events were observed; 72 in the two-dose group and 51 in the one-dose group, with no differences in severity (p=0·78) or outcomes (p=0·71) by study group. 12 (17%) events in the two-dose group and seven (14%) in the one-dose group were severe; most events were mild, resolved without sequelae, and were unrelated to the MR vaccine. One death occurred in the one-dose group before the infant received the 9-month dose of the vaccine, and therefore was deemed to be unrelated to the MR vaccine.
The data presented support use of MR vaccine at 6 months to protect young infants during measles outbreaks and in settings with increased risk or high transmission. We recommend additional studies to evaluate longer-term immunity based on age at vaccination.
US Centers for Disease Control and Prevention.
For the French and Spanish translations of the abstract see Supplementary Materials section.
作为标准两剂次免疫程序的一部分，麻疹风疹（MR）疫苗的第一剂通常在婴儿9月龄时接种。然而，在大规模麻疹疫情期间以及其他传播增加或风险升高的情况下，世界卫生组织建议在6月龄时接种一剂补充疫苗，以保护小婴儿。我们旨在评估6月龄婴儿接种第一剂MR疫苗的免疫原性和安全性，以及其对9月龄时常规MR疫苗免疫应答的影响。
这项开放标签随机试验纳入了孟加拉国马特莱地区6月龄健康婴儿，这些婴儿未曾接种过MR疫苗，且无麻疹或风疹病史。采用计算机生成的区组随机化方案，将婴儿随机分配（1:1）接受两剂MR疫苗，一剂在6月龄接种，另一剂在9月龄接种（两剂组），或仅在9月龄接种一剂（一剂组）。在所有入组参与者6月龄时记录基线特征。在每次接种前以及婴儿11月龄进行最终随访时采集血样进行抗体检测。主要结局是6月龄或9月龄婴儿第一剂MR疫苗的免疫原性，以及6月龄时接种第一剂MR疫苗的9月龄婴儿第二剂MR疫苗的免疫原性。免疫原性通过接种后6月龄12周内或9月龄8周内血清阳转婴儿的比例来衡量。血清阳转定义为IgG浓度相对于接种前浓度升高4倍，或在研究时间点之间达到血清保护性抗体浓度。改良意向性分析纳入了每组分配中接受MR疫苗接种且在基线、9月龄和11月龄有抗体结果的所有婴儿。所有入组婴儿均纳入即时反应（研究人员在固定地点诊所接种后前30分钟观察）、6月龄接受第一剂MR疫苗的两剂组婴儿接种后48小时内不良事件以及研究人员或家长在研究期间任何时间观察到的不良事件的安全性分析。该试验已在ClinicalTrials.gov注册，注册号为NCT03071575，现已结束入组。
2017年3月9日至2018年3月18日期间，620名婴儿入组并随机分配至两个研究组（两剂组312名，一剂组308名）。在6月龄接种疫苗的301名婴儿中，282名麻疹血清阳转（94%，95%CI 90-96），283名风疹血清阳转（94%，91-96）。到11月龄时，在9月龄接种第二剂后，297名（累计99%，95%CI 97-100）婴儿麻疹血清阳转，297名婴儿风疹血清阳转（累计99%，96-100）。仅在9月龄接种疫苗的292名婴儿中，到11月龄时291名两种抗原均血清阳转（100%，95%CI 98-100）。观察到123起不良事件；两剂组72起，一剂组51起，两组在严重程度（p=0·78）或结局（p=0·71）方面无差异。两剂组12起（17%）事件和一剂组7起（14%）事件为严重事件；大多数事件为轻度，无后遗症且与MR疫苗无关。一剂组有1名婴儿在接种9月龄疫苗剂量前死亡，因此被认为与MR疫苗无关。
所呈现的数据支持在6月龄时使用MR疫苗，以在麻疹疫情期间以及风险增加或传播率高的情况下保护小婴儿。我们建议开展更多研究以评估基于接种年龄的长期免疫情况。
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