Efficacy of FLU-v in an H1N1 Influenza Human Challenge Model
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      FLU-v is a broad spectrum influenza vaccine that targets regions conserved among multiple
      influenza strains. FLU-v adjuvanted with Montanide ISA-51 was shown to be safe in previous
      trials. This study aims to assess efficacy of adjuvanted FLU-v vaccine in protecting healthy
      volunteers against an influenza challenge delivered intranasally under quarantine.

      Efficacy of FLU-v will be assessed by measuring the incidence and severity of the disease in
      the treatment groups compared to the placebo group. In addition, the immune responses of the
      volunteers to FLU-v will also be explored.
    

Detailed description: 
      Influenza is a highly variable virus. Most of the variability comes from the proteins on the
      viral capsid surface; NA and HA. Current vaccines use these highly variable, immunogenic
      proteins to induce production of neutralising antibodies, however because these proteins are
      different for each strain, and can also change over time within strains due to antigenic
      drift, a new vaccine is required each year designed specifically to the strain predicted to
      circulate that year. In the event of a mismatch between predicted and actual circulating
      strains, or the emergence of a new strain due to antigenic shift, the effectiveness of the
      annual vaccine is drastically reduced. These limitations are further compounded by the short
      manufacturing window between strain prediction and the start of the influenza season, as well
      as the limited supply of suitable eggs used for vaccine production. As a result of these
      issues, only a limited supply of annual vaccine is available.

      FLU-v, a novel peptide vaccine, aims to provide a broad-spectrum response using peptide
      antigens matching immunogenic regions of conserved viral proteins found inside the viral
      capsid. These antigens have been shown to induce cytotoxic T-cell responses and
      non-neutralising antibodies in both pre-clinical and clinical studies. The FLU-v vaccine
      administered with and without adjuvant has been demonstrated to be safe in previous trials,
      and addition of adjuvant Montanide ISA-51 was shown to produce superior immunological
      responses compared to non-adjuvanted FLU-v. Data from a previous phase IIb study conducted as
      part of the UNISEC consortium suggest that the cellular and/or humoral responses resulting
      from vaccination with adjuvanted FLU-v may reduce influenza symptom severity and duration,
      although the study was not powered to assess these efficacy measures.

      Presently, efficacy will be evaluated as a primary endpoint alongside safety as part of a
      single centre, placebo controlled, phase IIb viral challenge study, using influenza A 2009
      H1N1 human virus, in suitable healthy subjects aged 18-60 years. Two dosing regimens will be
      explored. In addition, immunological endpoints will be addressed as exploratory endpoints.
    

Intervention name(s): adjuvanted FLU-v; adjuvanted placebo; Influenza challenge
Intervention type(s): Biological; Biological; Other
Intervention description(s): Subcutaneous injection in the upper arm with 500mcg of FLU-v as 0.5ml emulsion in 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51; Subcutaneous injection in the upper arm with 0.5ml emulsion made of 0.25ml of WFI and 0.25ml of adjuvant Montanide ISA-51; On day 0, administration with an intranasal sprayer of 1ml of PBS containing 10(7) TCID50 of Influenza A 2009 H1N1 human virus manufactured under GMP in certified Vero cells.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: broad; universal; vaccine; influenza; peptide; T cell; H1N1; human challenge