PMID- 32150750 OWN - NLM STAT- MEDLINE DCOM- 20200907 LR - 20200907 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 172 IP - 7 DP - 2020 Apr 7 TI - Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults: A Randomized Clinical Trial. PG - 453-462 LID - 10.7326/M19-0735 [doi] AB - 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 microg 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-gamma (IFN-gamma) 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-gamma-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P < 0.001) for tumor necrosis factor-alpha (TNF-alpha), 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-gamma and 5.7-fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-alpha 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. FAU - Pleguezuelos, Olga AU - Pleguezuelos O AD - SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.). FAU - Dille, Joep AU - Dille J AD - Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.). FAU - de Groen, Sofie AU - de Groen S AD - Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.). FAU - Oftung, Fredrik AU - Oftung F AD - Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.). FAU - Niesters, Hubert G M AU - Niesters HGM AD - University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands (H.G.N.). FAU - Islam, Md Atiqul AU - Islam MA AD - Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands, and Shahjalal University of Science and Technology, Sylhet, Bangladesh (M.A.I.). FAU - Naess, Lisbeth Meyer AU - Naess LM AD - Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.). FAU - Hungnes, Olav AU - Hungnes O AD - Norwegian Institute of Public Health, Oslo, Norway (F.O., L.M.N., O.H.). FAU - Aldarij, Nuhoda AU - Aldarij N AD - Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.). FAU - Idema, Demi L AU - Idema DL AD - Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.). FAU - Perez, Ana Fernandez AU - Perez AF AD - SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.). FAU - James, Emma AU - James E AD - SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.). FAU - Frijlink, Henderik W AU - Frijlink HW AD - Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.). FAU - Stoloff, Gregory AU - Stoloff G AD - SEEK, London, United Kingdom (O.P., A.F.P., E.J., G.S.). FAU - Groeneveld, Paul AU - Groeneveld P AD - Isala Hospital, Zwolle, the Netherlands (J.D., S.D., P.G.). FAU - Hak, Eelko AU - Hak E AD - Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands (N.A., D.L.I., H.W.F., E.H.). LA - eng SI - ClinicalTrials.gov/NCT02962908 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200310 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Antibodies, Viral) RN - 0 (Influenza Vaccines) RN - 0 (Vaccines, Synthetic) SB - IM MH - Adult MH - Antibodies, Viral/blood MH - Dose-Response Relationship, Immunologic MH - Double-Blind Method MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Humans MH - Immunity, Cellular MH - Influenza Vaccines/*adverse effects/*immunology MH - Influenza, Human/*prevention & control MH - Male MH - Middle Aged MH - Netherlands MH - Patient Safety MH - Vaccines, Synthetic/*adverse effects/*immunology EDAT- 2020/03/10 06:00 MHDA- 2020/09/08 06:00 CRDT- 2020/03/10 06:00 PHST- 2020/03/10 06:00 [pubmed] PHST- 2020/09/08 06:00 [medline] PHST- 2020/03/10 06:00 [entrez] AID - 2762723 [pii] AID - 10.7326/M19-0735 [doi] PST - ppublish SO - Ann Intern Med. 2020 Apr 7;172(7):453-462. doi: 10.7326/M19-0735. Epub 2020 Mar 10.