Universal influenza vaccine one step closer to reality
Adjuvanted FLU-v, a broad-spectrum influenza vaccine that induces antibodies and cell-mediate immunity, has demonstrated immunogenicity in a phase IIb trial, warranting phase III development to explore its safety and efficacy.
This randomized, double-blind, placebo-controlled, single-centre clinical trial randomly assigned 175 healthy adults aged 18–60 years to 0.5-mL subcutaneous infection of 500 µg of adjuvanted (one dose) or nonadjuvanted (two doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo).
The investigators used flow cytometry and enzyme-linked immunosorbent assay to assess vaccine-specific cellular responses at days 0, 42 and 180. They also collected solicited information on adverse events (AEs) for 21 days after vaccination and unsolicited information on AEs throughout the study.
Mild-to-moderate injection site reactions were the most common AEs. The difference in median fold increase in secreted interferon-γ (IFN-γ) between A-FLU-v and A-placebo was 38.2-fold (95 percent confidence interval [CI], 4.7–69.7; p=0.001) at day 42 and 25.0-fold (95 percent CI, 5.7–50.9; p<0.001) at day 180.
At day 42, differences in median fold increase between A-FLU-v and A-placebo were 4.5-fold (95 percent CI, 2.3–9.8; p<0.001) for IFN-γ–producing CD4+ T cells, 4.9-fold (95 percent CI, 1.3–40.0; p<0.001) for tumour necrosis factor-α (TNF-α), 7.0-fold (95 percent CI, 3.5–18.0; p<0.001) for interleukin-2 (IL-2), and 1.7-fold (95 percent CI, 0.1–4.0; p=0.004) for CD107a.
At day 180, differences were 2.1-fold (95 percent CI, 0.0–6.0; p=0.030) for IFN-γ and 5.7-fold (95 percent CI, 2.0–15.0; p<0.001) for IL-2, with no difference for TNF-α or CD107a.
There were no differences observed between NA-FLU-v and NA-placebo.
“The study was not powered to evaluate vaccine efficacy against influenza infection,” the investigators noted.