Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background

Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination.

Methods

We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467.

Findings

Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (

Interpretation

The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic.

Funding

French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

OL reports grant from French ministry of health and grants or contracts from Pfizer, Sanofi-Pasteur, GSK, MSD, AstraZeneca and Janssen. CJ reports fees for boardmembership from AstraZeneca, Pfizer and MSD. TS reports grant from DGOS (French Ministry of health), AstraZeneca, Bayer, Novartis, Sanofi, Boehringer, Daiichi Sankyo, Eli Lilly, GSK and personal fees for boardmembership and consulting from various pharmaceutical companies, including AstraZeneca, Sanofi, Bayer, Ablative Solutions and 4 Living Biotech. KL reports personal fees from Gilead, MSD, Janssen, ViiV, Spikimm and fees for development of educational presentations from Janssen, Gilead, MSD, Sobi, and Chiesi. PL reports personal fees for board membership from Pfizer, Janssen, AstraZeneca, MSD, Viiv, GSK, consultancy and travel accommodation from Pfizer. EBN has received grant pending from Sanofi Pasteur and fees for board membership from Pfizer, and Janssen. MB reports travels grants from various pharmaceutical companies, including Pfizer, Novex, Janssen. XDL reports research grant from INSERM.