Intranasal Modified Vacc-4x Gag Peptides With Endocine as Adjuvant
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      HIV-specific cellular immunity is hampered in most HIV-infected individuals. Therapeutic
      immunization in HIV aims to strengthen the HIV-specific cellular immunity, usually in the
      absence of replicating HIV with antiretroviral drugs. The aims of this strategy can be to
      decrease the mass of latently infected CD4+ T cells, better tolerance of drug-free periods,
      and better select candidates for preventive HIV vaccines.

      Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four,
      slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal
      injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found
      improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the
      AIDS vaccine 2011 conference, Bangkok).

      In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal
      mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal
      adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both
      systemically and at mucosal surfaces (oral, rectal, vaginal).
    

Detailed description: 
      HIV-specific cellular immunity is hampered in most HIV-infected individuals, partly because
      the virus infects CD4+ T cells, the key cell subset in all immune responses. CD4 is the
      primary HIV receptor (CD4), but infection requires a co-receptor (CCR5) which is carried
      mainly by activated T cells. During primary HIV-infection, two types of CD4+ T cells mainly
      become infected: (i) Sub-activated T cells of all specificities within the mucosal linings,
      particularly in the gut; and (ii) HIV-specific T cell clones, that proliferates and are
      activated as a normal response to HIV infection itself. The HIV-specific immunity therefore
      becomes severely compromised early in the infection. Patients having better T cells specific
      to parts of the HIV Gag matrix protein usually progress slower towards AIDS than patients
      with poor T cell responsitivity towards Gag.

      Therapeutic immunization in HIV aims to strengthen the HIV-specific cellular immunity,
      usually in the absence of replicating HIV with antiretroviral drugs. The aims of this
      strategy can be to decrease the mass of latently infected CD4+ T cells, better tolerance of
      drug-free periods, and better select candidates for preventive HIV vaccines. The latter point
      may be important since clinical trials with preventive vaccine candidates may challenge our
      ethical standards: Such trials must be very large and conducted in poor areas with high
      prevalence of HIV, in order to have as many (placebo) or few (vaccine candidate) new HIV
      infections as fast as possible. Preventive vaccine trials might therefore compete with
      introduction of "western" access to HIV drugs.

      Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four,
      slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal
      injections using GM-CSF as adjuvant. In a dose study at our Hospital, the investigators found
      induction of robust cellular immune responses both in vitro and in vivo by skin testing,
      indications of improved viral control, long-lasting immunity and lack of mutational changes
      in the HIV strains within the study cohort. A recently completed multinational
      placebo-controlled study found improvement of viral loads (presented at the AIDS vaccine 2011
      conference, Bangkok).

      In this study the investigators hypothesize that the Vacc-4x peptides, deposited on the nasal
      mucosal surfaces in conjunction with Endocine, a newly developed and documented mucosal
      adjuvant, will induce T cell responses to HIV and improve HIV-specific immunity both
      systemically and at mucosal surfaces (oral, rectal, vaginal). This route of application may
      even simplify mass vaccination. The study is primarily a dose-study focused on adverse
      events, which have been negligible when Vacc-4x was given parenterally, as well as induction
      of systemic and mucosal immunity.
    

Intervention name(s): Vacc-4x low dose; Vacc-4x medium dose; Vacc-4x high dose; Zero dose
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): 80 µg Vacc-4x (20 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks; 400 µg Vacc-4x (100 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks; 1200 µg Vacc-4x (300 µg pr. peptide) in 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks; 300 µl Endocine divided into two administrations, one for each nose cavity, administrated once weekly for four weeks
Other intervention name(s): Vacc-4x; Endocine; Vacc-4x; Endocine; Vacc-4x; Endocine; Endocine
Intervention MeSH terms: Endocine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: HIV; vaccination; T cells; mucosal immunity; safety; nasal administration; DTH skin test