Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults

Olga Pleguezuelos*, Joep Dille, Sofie de Groen, Fredrik Oftung, Hubert G. M. Niesters, Md Atiqul Islam, Lisbeth Meyer Naess, Olav Hungnes, Nuhoda Aldarij, Demi L. Idema, Ana Fernandez Perez, Emma James, Henderik W. Frijlink, Gregory Stoloff, Paul Groeneveld, Eelko Hak

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)


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. ( NCT02962908; Eudra CT: 2015-001932-38)

Setting: The Netherlands.

Participants: 175 healthy adults aged 18 to 60 years.

Intervention: 0.5-mL subcutaneous injection of 500 mu g 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.

Original languageEnglish
Pages (from-to)453-462
Number of pages15
JournalAnnals of Internal Medicine
Issue number7
Publication statusPublished - 7-Apr-2020


  • MICE

Cite this