• Olga Pleguezuelos, Joep Dille, Sofie de Groen, Fredrik Oftung, Niesters Hubert G M HGM University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands (H.G.N.)., Md Atiqul Islam, Lisbeth Meyer Næss, Olav Hungnes, Nuhoda Aldarij, Demi L Idema, Ana Fernandez Perez, Emma James, Henderik W Frijlink, Gregory Stoloff, Paul Groeneveld, and Eelko Hak.
• SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.).
• Ann. Intern. Med. 2020 Apr 7; 172 (7): 453-462.

BackgroundFLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity.ObjectiveTo compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo.DesignRandomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; EudraCT: 2015-001932-38).SettingThe Netherlands.Participants175 healthy adults aged 18 to 60 years.Intervention0.5-mL subcutaneous injection of 500 µg of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo) (2:2:1:1 ratio).MeasurementsVaccine-specific cellular responses at days 0, 42, and 180 were assessed via flow cytometry and enzyme-linked immunosorbent assay. Solicited information on adverse events (AEs) was collected for 21 days after vaccination. Unsolicited information on AEs was collected throughout the study.ResultsThe AEs with the highest incidence were mild to moderate injection site reactions. The difference between A-FLU-v and A-placebo in the median fold increase in secreted interferon-γ (IFN-γ) was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = 0.001) at day 42 and 25.0-fold (CI, 5.7- to 50.9-fold; P < 0.001) at day 180. The differences between A-FLU-v and A-placebo in median fold increase at day 42 were 4.5-fold (CI, 2.3- to 9.8-fold; P < 0.001) for IFN-γ-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P < 0.001) for tumor necrosis factor-α (TNF-α), 7.0-fold (CI, 3.5- to 18.0-fold; P < 0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) for CD107a. At day 180, differences were 2.1-fold (CI, 0.0- to 6.0-fold; P = 0.030) for IFN-γ and 5.7-fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-α or CD107a. No differences were seen between NA-FLU-v and NA-placebo.LimitationThe study was not powered to evaluate vaccine efficacy against influenza infection.ConclusionAdjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy.Primary Funding SourceSEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.

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