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Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial.

The Lancet regional health. Europe

Authors: Elisabeth A Dulfer, Büsra Geckin, Esther J M Taks, Corine H GeurtsvanKessel, Helga Dijkstra, Liesbeth van Emst, Christa E van der Gaast-de Jongh, Djenolan van Mourik, Petra C Koopmans, Jorge Domínguez-Andrés, Reinout van Crevel, Josephine S van de Maat, Marien I de Jonge, Mihai G Netea

BACKGROUND: Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity.

METHODS: TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands. Individuals ≥60 years, fully vaccinated against COVID-19 were eligible for participation and randomized into one of four study groups: 1) 0.5 ml influenza vaccination Vaxigrip Tetra followed by 0.3 ml BNT162b2 COVID-19 booster vaccination 21 days later, (2) COVID-19 booster vaccination followed by influenza vaccination, (3) influenza vaccination concurrent with the COVID-19 booster vaccination, and (4) COVID-19 booster vaccination only (reference group). Primary outcome was the geometric mean concentration (GMC) of IgG against the spike (S)-protein of the SARS-CoV-2 virus, 21 days after booster vaccination. We performed a non-inferiority analysis of concurrent administration compared to booster vaccines alone with a predefined non-inferiority margin of -0.3 on the log10-scale.

FINDINGS: 154 individuals participated from October, 4, 2021, until November, 5, 2021. Anti-S IgG GMCs for the co-administration and reference group were 1684 BAU/ml and 2435 BAU/ml, respectively. Concurrent vaccination did not meet the criteria for non-inferiority (estimate -0.1791, 95% CI -0.3680 to -0.009831) and antibodies showed significantly lower neutralization capacity compared to the reference group. Reported side-effects were mild and did not differ between study groups.

INTERPRETATION: Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this.

TRIAL REGISTRATION NUMBER: EudraCT: 2021-002186-17.

FUNDING: The study was supported by the ZonMw COVID-19 Programme.

© 2023 The Author(s).

PMID: 37261212

Participating cluster members