FLU-v is comprised of four synthetic peptides predicted in silico to cover heavily conserved immunogenic regions of influenza A and B viral proteins M1, M2 and NP-A and NP-B. These internal viral proteins evolve more slowly than the surface proteins traditionally targeted by classical influenza vaccines, which require updating every year.
The FLU-v vaccine aims to elicit a broadly protective immune response through viral clearance by cytotoxic T cell release of pro-inflammatory cytokines, as well as perforin and granzyme.
FLU-v has demonstrated safety, immunogenicity, and clinical efficacy in preclinical work and in Phase I and Phase II clinical studies. A Phase IIb H1N1 challenge trial in healthy adults observed a significant reduction in mild to moderate cases of influenza disease and fewer participants reporting two or more symptoms with FLU-v, compared to placebo.
Having met clinical efficacy and safety endpoints in Phase 1 and Phase 2 studies, FLU-v is now ready for Phase 3 development.
FLU-v clinical development
Phase 1b safety and immuno study (Pleguezuelos et al, 2012, Vaccine)
Phase 1b H3N2 challenge study (Pleguezuelos et al, 2015, Clin Vaccine Immunol)
Phase 2b field study (Pleguezuelos et al, 2020, Annals of Internal Medicine)
Phase 2b H1N1 challenge study (Pleguezuelos et al, 2020, NPJ Vaccines)
FLU-v manufacture and storage
FLU-v vaccine peptides are synthesised using the egg-free Fmoc chemistry process and can be shipped and stored at room temperature in API lyophilised powder form for 3 months (up to 2 years at 20°C). The powder is then combined with non-metal based MontanideTM ISA-51 adjuvant and water for injection immediately prior to use.
Stoloff GA, Caparros-Wanderley W. Synthetic multi-epitope peptides identified in silico induce protective immunity against multiple influenza serotypes. Eur J Immunol, 2007, 37:9, 2441-9. doi: 10.1002/eji.200737254
Pleguezuelos et al. Synthetic Influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled Phase I trial. Vaccine, 2012, 30:31, 4655-4660. doi: 10.1016/j.vaccine.2012.04.089
Pleguezuelos et al. A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clin Vaccine Immunol., 2015, 22:7; 828-35. doi: 10.1128/CVI.00098-15.
Pleguezuelos et al. Immunogenicity, safety, and efficacy of a standalone universal influenza vaccine, FLU-v, in healthy adults. Annals of Internal Medicine, 2020, 172:7, 453-462. doi:10.7326/M19-0735
Pleguezuelos et al. Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study. NPJ Vaccines, 2020, 5:22, doi: 10.1038/s41541-020-0174-9