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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
22 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number100628
JournalThe Lancet Regional Health - Europe
Volume29
DOIs
Publication statusPublished - Jun 2023

Bibliographical note

Funding Information:
The study was supported by the COVID-19 Programme of ZonMw . MGN was supported by an ERC Advanced Grant (# 833247 ) and a Spinoza Grant of the Netherlands Organisation for Scientific Research .

Publisher Copyright:
© 2023 The Author(s)

Fingerprint

Dive into the research topics of 'Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial'. Together they form a unique fingerprint.

Cite this