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

Prins, M.L.M.; Roozen, G.V.T.; Pothast, C.R.; Huisman, W.; Binnendijk, R. van; Hartog, G. den; Kuiper, V.P.; Prins, C.; Janse, J.J.; Lamers, O.A.C.; Koopman, J.P.R.; Kruithof, A.C.; Kamerling, I.M.C.; Dijkland, R.C.; Kroon, A.C. de; Azimi, S.; Feltkamp, M.C.W.; Kuijer, M.; Jochems, S.P.; Heemskerk, M.H.M.; Rosendaal, F.R.; Roestenberg, M.; Visser, L.G.; Roukens, A.H.E.

doi: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 naive 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 naive participants, aged 18-30 years, were randomized (1:1:1) to receive either two doses of 20 mu g mRNA-1273 ID with a standard needle (SN) or the Bella-mu (R) needle (BM), or two doses of 100 mu g 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%...Show moreFractional 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 naive 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 naive participants, aged 18-30 years, were randomized (1:1:1) to receive either two doses of 20 mu g mRNA-1273 ID with a standard needle (SN) or the Bella-mu (R) needle (BM), or two doses of 100 mu g 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.Show less

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