Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults: A Randomized Clinical Trial.

Autor:	Pleguezuelos O; SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.)., Dille J; Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.)., de Groen S; Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.)., Oftung F; Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.)., Niesters HGM; University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands (H.G.N.)., Islam MA; Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands, and Shahjalal University of Science and Technology, Sylhet, Bangladesh (M.A.I.)., Næss LM; Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.)., Hungnes O; Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.)., Aldarij N; Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.)., Idema DL; Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.)., Perez AF; SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.)., James E; SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.)., Frijlink HW; Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.)., Stoloff G; SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.)., Groeneveld P; Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.)., Hak E; Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.).
Jazyk:	angličtina
Zdroj:	Annals of internal medicine [Ann Intern Med] 2020 Apr 07; Vol. 172 (7), pp. 453-462. Date of Electronic Publication: 2020 Mar 10.
DOI:	10.7326/M19-0735
Abstrakt:	Background: FLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity. Objective: To compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo. Design: Randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; EudraCT: 2015-001932-38). Setting: The Netherlands. Participants: 175 healthy adults aged 18 to 60 years. Intervention: 0.5-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). Measurements: Vaccine-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. Results: The 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. Limitation: The study was not powered to evaluate vaccine efficacy against influenza infection. Conclusion: Adjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy. Primary Funding Source: SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.
Databáze:	MEDLINE
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