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

doi:10.1016/j.lanepe.2023.100628

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

Lancet Reg Health Eur. 2023 Apr 12:29:100628. doi: 10.1016/j.lanepe.2023.100628. eCollection 2023 Jun.

Authors

Elisabeth A Dulfer^{1

2}, Büsra Geckin^{1

2}, Esther J M Taks^{1

2}, Corine H GeurtsvanKessel³, Helga Dijkstra^{1

2}, Liesbeth van Emst^{1

2}, Christa E van der Gaast-de Jongh^{2

4}, Djenolan van Mourik³, Petra C Koopmans⁵, Jorge Domínguez-Andrés^{1

2}, Reinout van Crevel^{1

2}, Josephine S van de Maat^{1

2}, Marien I de Jonge^{2

4}, Mihai G Netea^{1

2

6}

Affiliations

¹ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
² Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
³ Laboratory of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
⁴ Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁵ Department of Biostatistics, Radboud University Medical Center, Nijmegen, the Netherlands.
⁶ Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Germany.

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.

Keywords: COVID-19; Infection; Infectious diseases; Influenza; SARS-CoV2; Vaccines; mRNA.

Grants and funding

833247/ERC_/European Research Council/International