Prins Manon L M, Roozen Geert V T, Pothast Cilia R, Huisman Wesley, van Binnendijk Rob, den Hartog Gerco, Kuiper Vincent P, Prins Corine, Janse Jacqueline J, Lamers Olivia A C, Koopman Jan Pieter R, Kruithof Annelieke C, Kamerling Ingrid M C, Dijkland Romy C, de Kroon Alicia C, Azimi Shohreh, Feltkamp Mariet C W, Kuijer Marjan, Jochems Simon P, Heemskerk Mirjam H M, Rosendaal Frits R, Roestenberg Meta, Visser Leo G, Roukens Anna H E
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
NPJ Vaccines. 2024 Jan 2;9(1):1. doi: 10.1038/s41541-023-00785-w.
Fractional dosing can be a cost-effective vaccination strategy to accelerate individual and herd immunity in a pandemic. We assessed the immunogenicity and safety of primary intradermal (ID) vaccination, with a 1/5th dose compared with the standard intramuscular (IM) dose of mRNA-1273 in SARS-CoV-2 naïve persons. We conducted an open-label, non-inferiority, randomized controlled trial in the Netherlands between June and December 2021. One hundred and fifty healthy and SARS-CoV-2 naïve participants, aged 18-30 years, were randomized (1:1:1) to receive either two doses of 20 µg mRNA-1273 ID with a standard needle (SN) or the Bella-mu® needle (BM), or two doses of 100 µg IM, 28 days apart. The primary outcome was non-inferiority in seroconversion rates at day 43 (D43), defined as a neutralizing antibody concentration threshold of 465 IU/mL, the lowest response in the IM group. The non-inferiority margin was set at -15%. Neutralizing antibody concentrations at D43 were 1789 (95% CI: 1488-2150) in the IM and 1263 (951-1676) and 1295 (1020-1645) in the ID-SN and ID-BM groups, respectively. The absolute difference in seroconversion proportion between fractional and standard-dose groups was -13.95% (-24.31 to -3.60) for the ID-SN and -13.04% (-22.78 to -3.31) for the ID-BM group and exceeded the predefined non-inferiority margin. Although ID vaccination with 1/5th dose of mRNA-1273 did not meet the predefined non-inferior criteria, the neutralizing antibody concentrations in these groups are far above the proposed proxy for protection against severe disease (100 IU/mL), justifying this strategy in times of vaccine scarcity to accelerate mass protection against severe disease.
在大流行期间，分剂量接种可以成为一种具有成本效益的疫苗接种策略，以加速个体和群体免疫。我们评估了在未感染过严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的人群中，与标准肌肉注射（IM）剂量的mRNA-1273相比，五分之一剂量的皮内（ID）初次接种疫苗的免疫原性和安全性。2021年6月至12月期间，我们在荷兰进行了一项开放标签、非劣效性、随机对照试验。150名年龄在18至30岁之间、健康且未感染过SARS-CoV-2的参与者被随机分为三组（1:1:1），分别接受两剂20μg的mRNA-1273，采用标准针头（SN）或贝拉穆®针头（BM）进行皮内注射，或两剂100μg的肌肉注射，间隔28天。主要结局是在第43天（D43）的血清转化率非劣效性，定义为中和抗体浓度阈值为465IU/mL，这是肌肉注射组的最低反应。非劣效性界限设定为-15%。IM组在D43时的中和抗体浓度为1789（95%置信区间：1488-2150），ID-SN组和ID-BM组分别为1263（951-1676）和1295（1020-1645）。分剂量组与标准剂量组之间血清转化率的绝对差异，ID-SN组为-13.95%（-24.31至-3.60），ID-BM组为-13.04%（-22.78至-3.31），超过了预先设定的非劣效性界限。虽然接种五分之一剂量的mRNA-1273皮内疫苗未达到预先设定的非劣效标准，但这些组中的中和抗体浓度远高于针对严重疾病的建议保护替代值（100IU/mL），这证明在疫苗短缺时期采用这种策略来加速针对严重疾病的大规模保护是合理的。
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