The adjuvanted, broad-spectrum influenza vaccine FLU-v was found to be immunogenic and merits phase 3 development to explore efficacy, according to data published in Annals of Internal Medicine.
A randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial was performed in the Netherlands (ClinicalTrials.gov Identifier: NCT02962908). The trial included 175 healthy adults aged 18 to 60 years. Participants received a 0.5-mL subcutaneous injection of 500 µg of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v or adjuvanted or nonadjuvanted placebo in a 2:2:1:1 ratio.
The difference in median fold increase secreted interferon- γ (IFN-γ) between adjuvanted-FLU-v and adjuvanted-placebo was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = .001) at day 42 and 25.0-fold (95% CI, 5.7- to 50.9-fold; P < .001) at day 180. For IFN-γ-producing CD4+ T cells, the differences between adjuvanted-FLU-v and adjuvanted-placebo in median fold increase at day 42 were 4.5-fold (95% CI, 2.3- to 9.8-fold; P < .001). This trend continued through day 180, with a 4.4-fold [CI, 1.0- to 7.8-fold] increase from baseline. Similarly, IL-2 (6.5-fold [CI, 2.1- to 10.9- fold] vs 0.0-fold [CI, 0.1- to 0.1-fold]).
There was a 4.9-fold (95% CI, 1.3- to 40.0-fold; P < .001) increase for tumor necrosis factor-α (TNF-α), 7.0-fold (95% CI, 3.5- to 18.0-fold; P < .001) for interleukin-2 (IL-2), and 1.7-fold (95% CI, 0.1- to 4.0-fold; P = .004) for CD107a. At day 180, differences were 2.1-fold (95% CI, 0.0- to 6.0-fold; P = .030) for IFN-γ and 5.7-fold (95% CI, 2.0- to 15.0-fold; P < .001) for IL-2. There were no differences for TNF-α or CD107a.
There were no differences were seen between nonadjuvanted-FLU-v and nonadjuvanted-placebo. The highest incidences of adverse events were mild to moderate injection site reactions.
Pain at the injection site was the only severe adverse event that occurred in > 5% of participants in the single-dose A-FLU-v group (n=3). There were 5 serious adverse events recorded, none of which were considered to be related to the vaccine.
Investigators noted that the study was not powered to evaluate vaccine efficacy against infection. However, the data did show, “a single dose of [adjuvanted]-FLU-v elicited cell-mediated and humoral immune responses to FLU-v antigens.” Therefore, they concluded that further development is warranted for a single dose to be tested in a phase 3 setting with a larger cohort of vaccines. In doing so, efficacy and safety can be further explored as the primary endpoints.
Disclaimer: This study was funded by SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project.
Pleguezuelos O, Dille J, de Groen S, et al. Immunogenicity, safety, and efficacy of a standalone universal influenza vaccine, FLU-v, in healthy adults: A randomized clinical trial [published online March 10 2020. Ann Intern Med. doi: 10.7326/M19-0735