Immunogenicity and reactogenicity of intradermal mRNA-1273 SARS-CoV-2 vaccination: a non-inferiority, randomized-controlled trial

Journal article

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.

Authors: Prins, MLM; Roozen, GVT; Pothast, CR; Huisman, W; van Binnendijk, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: npj Vaccines
• Volume: 9
• Issue: 1
• Pages: 1-1
• Article number: 1
• Publication date: 2024-01-02
• Acceptance date: 2023-11-15
• DOI: 10.1038/s41541-023-00785-w
• EISSN: 2059-0105
• ISSN: 2059-0105
• Language: English
• Keywords: Dosing; Randomized controlled trial; Gastroenterology; Seroconversion; Internal medicine; Antibody; Medicine; Vaccination; Immunology; Reactogenicity; Immunogenicity