A Phase I Study to Assess the Safety and Immunogenicity of Tuberculosis (TB) Vaccine Candidates FP85A and MVA85A
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I study whose primary outcome is to assess the safety of a new tuberculosis
      vaccine, FP85A, when administered individually and sequentially with MVA85A in a prime-boost
      regime, to healthy volunteers, who have previously been vaccinated with BCG. The secondary
      outcome is to assess the cellular immune response in the same population. The trial consists
      of 36 subjects in 3 groups. The first group will be vaccinated with FP85A alone, the second
      group will be vaccinated with MVA85A followed by FP85A 28 days later and the third group will
      be vaccinated with FP85A followed by MVA85A 28 days later.
    

Detailed description: 
      Recombinant fowlpox virus as a vector

      Fowlpox virus is only infectious to avian species, but it is able to express antigens in
      mammalian cells and induce protective immune responses, making it a suitable candidate
      vector. Recombinant fowlpox viruses have been developed that express antigens from tumour
      cells, HIV and malaria. FP9 is a live, highly attenuated form of a European strain of fowlpox
      virus. It was derived from multiple passages in avian cells, followed by plaque purification
      and the genome has been fully characterised. Fowlpox virus was initially used as a
      recombinant avian vaccine, but it has also been shown to be a potent inducer of CD8+T cells
      in preclinical mammalian models and in human trials . In fact, FP9 was found to be more
      immunogenic than wild type fowlpox and, when used with recombinant MVA in a prime boost
      regime induced a protective immune response against Plasmodium berghi.

      Clinical experience with recombinant fowlpox viruses in Oxford Three FP vaccines encoding
      different malaria antigens have been used so far in clinical trials in Oxford, FP9 ME-TRAP,
      FP9 CS and FP9 PP. To date 87 doses of FP9 ME-TRAP have been given to 55 volunteers in Oxford
      using various regimens in combination with DNA as well as recombinant MVA vaccines. The local
      and systemic safety profile of FP9 ME-TRAP is comparable to that described for recombinant
      MVA vaccines. No vaccine-related serious adverse events have been observed. Pain and erythema
      at the injection site are the predominant local side effects, with the erythema being maximal
      within 2 to 3 days post-vaccination before receding. The commonest systemic side effect after
      FP9 ME-TRAP is of feeling feverish although this is not always associated with a documented
      fever. Other solicited side effects are myalgia, arthralgia, headache and nausea. FP9 CS has
      been used recently in a phase I study in 25 healthy volunteers in Oxford, at doses of 1x10^8
      pfu. Analysis of safety and tolerability suggests similar side effect profile to FP9 ME-TRAP.
      No serious adverse events were noted in the study. In a phase I/IIa study which is nearing
      completion, 15 volunteers were immunised with 5x10^7 pfu of FP9 PP, with no vaccine-related
      serious adverse events and comparable adverse events.
    

Intervention name(s): FP85A; MVA85A
Intervention type(s): Biological; Biological
Intervention description(s): Recombinant Fowlpox virus 9 expressing antigen 85A from M. tuberculosis (5 x10^7 pfu); Modified vaccinia virus Ankara expressing antigen 85A from M. tuberculosis (5 x 10^7 pfu)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention