Investigating Immunisation Strategies of DNA, MVA and CN54rgp140 Adjuvanted With GLA-AF to Maximise Antibody Responses
Condition: HIV
Study type: Interventional
Phase: Phase 1

Summary: 
      UKHVC Spoke 003 is a randomised Phase I, two centre study which will explore the impact of
      shortening a vaccination regimen using deoxyribonucleic acid (DNA) (CN54ENV and ZM96GPN),
      Modified Vaccinia Ankara - C (MVA-C) and CN54rgp140 adjuvanted with glucopyranosyl lipid A
      adjuvant - aqueous form (GLA-AF). The study population will be 40 healthy male and female
      volunteers 18 to 45 years old who are at low risk of HIV infection are to be recruited.

      Study participants will be immunised with trial immunogens:

        -  8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone
           and one plasmid encoding gp140 env derived from clade C 97CN54

        -  1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins
           derived from clade-C 97CN54

        -  100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54

        -  5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant

      All immunisations will be administered by the intramuscular route (IM). CN54gp140 and GLA
      will be mixed together before administration, and immunogens will be delivered in combination
      regimens
    

Detailed description: 
      This is a phase I study exploring the safety and potency of five HIV vaccines in healthy
      volunteers. The main aim is to see whether three of the five vaccines can be given together
      rather than one after the other, in five rather than seven sets of vaccinations and a course
      shortened by eight weeks. All volunteers will receive three injections of the first two
      vaccines (DNA plasmids) and half will be randomly assigned to receive two injections each of
      the second (MVA-C) and subsequent vaccines (CN54rgp140 mixed with GLA-AF) during the same
      visit or two injections of the MVA-C followed by two of CN54rgp140 mixed with GLA-AF.

      The investigators are interested in ensuring that the vaccines are safe and also that the
      immune responses in the two groups of volunteers are similar. The three vaccines have all
      been shown to stimulate the immune response to specific parts of the HIV virus and none are
      infectious. The first vaccine consists of two DNA plasmids. When injected into muscle cells
      small parts of the HIV virus which are encoded by the DNA are produced and these are then
      recognised by the immune system. The second vaccine MVAC, is derived from vaccinia virus
      which has been modified so that it cannot divide. The virus (Modified Vaccinia Ankara (MVA))
      actually expresses the same portions of HIV as the DNA and results in amplification of the
      responses seen. The third vaccine is a synthetically produced component of the HIV viral
      outer coat and it will be administered with an additive which has been shown to greatly
      enhance particular types of immune response which have recently been shown to play a role in
      protection against infection
    

Intervention name(s): DNA; MVA-C; CN54rgp140; GLA-AF
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): 8mg DNA: one plasmid encoding a gag-pol-nef polypeptide derived from the 96ZM651-8 clone and one plasmid encoding gp140 env derived from clade C 97CN54; 1.108 TCID50 MVA-C (nominal titre) expressing the gag-pol-nef and gp120 env proteins derived from clade C 97CN54; 100ug CN54rgp140, a trimeric recombinant envelope protein derived from clade C 97CN54; 5ug GLA-AF, an aqueous glucopyranosyl lipid A adjuvant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV; Vaccine; Immunisation; DNA; Adverse events; MVA-C; GLA-AF; Antibody