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. 2023 Apr 12:29:100628.
doi: 10.1016/j.lanepe.2023.100628. eCollection 2023 Jun.

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

Elisabeth A Dulfer  1   2 , Büsra Geckin  1   2 , Esther J M Taks  1   2 , Corine H GeurtsvanKessel  3 , Helga Dijkstra  1   2 , Liesbeth van Emst  1   2 , Christa E van der Gaast-de Jongh  2   4 , Djenolan van Mourik  3 , Petra C Koopmans  5 , 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

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

Elisabeth A Dulfer et al. Lancet Reg Health Eur. .

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.

PubMed Disclaimer

Conflict of interest statement

MGN is a scientific founder of TTxD, Lemba and BioTrip, and a member of the TTxD scientific advisory board. MGN has received research grants from TTxD and GSK. The other authors have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Study design.
Fig. 2
Fig. 2
Geometric mean concentrations (with 95% error bars) of IgA and IgG antibodies against S-protein and RBD over the course of the study. a: anti-S IgG; b: anti-S IgA; c: anti-RBD IgG; d: anti-RBD IgA.
Fig. 3
Fig. 3
50% plaque-reducing neutralization titers (PRNT-50) for the D614G, delta and omicron variant of the SARS-CoV-2 virus, compared between all groups at 42 days after first study vaccinations (Visit 3).
Fig. 4
Fig. 4
Hemagglutinin inhibition (HAI) titers against the H1N1pdm influenza virus at 21 days after influenza vaccination (groups ‘influenza first’, ‘booster first’, ‘combination’ and 'booster only').
Fig. 5
Fig. 5
a): Principal component analysis of plasma proteins at 42 days after first study vaccine. (b–e): Volcano plot with fold changes of proteins in all four groups, 42 days after first study vaccine compared to baseline. b): Booster first. c): Influenza first. d): Combination. e): booster only.
Supplementary Fig. S1
Supplementary Fig. S1
Supplementary Fig. S6
Supplementary Fig. S6
See this image and copyright information in PMC

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