A Phase-I Study of a Nanoparticle-based Peptide Vaccine Against Dengue Virus
Condition: Dengue
MeSH terms: Dengue
Study type: Interventional
Phase: Phase 1

Summary: 
      This trial aims to test the safety of 2 doses of a T-cell priming specific cocktail of Dengue
      viruses peptides representing all 4 DENV serotypes and mounted on a gold nanoparticle.

      NOTE: This is the master protocol of a prospective 2-stage adaptive trial, which aims to add
      and test a Coronavirus vaccine candidate as well, in an identical trial design.
    

Detailed description: 
      A critical limitation for Dengue vaccines is their association with antibody-dependent
      enhancement, where poorly formed immune responses predispose the individual to severe disease
      during a second infection. Thus, a more targeted vaccine (inducing / priming T cells and not
      producing antibodies) could be the best alternative and most successful preventive method in
      the fight against severe manifestations of the disease.

      Nanoparticle antigen delivery systems have been developed to enrich specific targeting of
      immune receptors. These carrier systems are designed to facilitate antigen uptake and
      processing by antigen presenting cells (APCs), as well as to control antigen release and
      protect them from premature proteolytic degradation. This more targeted response also allows
      us to reduce the effective antigen dose (to nanomoles) and mimic a replicating infection with
      zero risk of developing the infectious disease.

      The hypotheses are listed below:

        1. During the COVID-19 pandemic, Dengue virus disease is likely to cause significant
           diagnostic confusion and it risks further progression due to disrupted control measures.

        2. As the SARS-CoV-2 pandemic devastates the world, the need for highly efficient and
           scalable vaccines is desperately required.

        3. Peptide vaccines have high potential as a rapidly scalable modular platform for emerging
           diseases requiring targeted immunological responses.

        4. Dengue viruses and Coronaviruses (e.g. COVID-19 causing viruses) are particularly well
           suited to this approach.

      For this initial naNO-DENGUE part of the trial, the objectives are as follows:

      Primary:

      To evaluate the safety and reactogenicity of two intradermal injections of two different
      doses of the investigational Dengue peptide T cell inducing vaccine (PepGNP-Dengue)
      administered to healthy volunteers as a:

        1. candidate vaccine for the prevention of Dengue

        2. proof-of-concept for a rapidly scalable modular peptide vaccine platform, which will be
           followed by a COVID-19 construct after interim analyses.

      Secondary:

        1. To assess the evidence of a T-cell mediated immune response as a surrogate of protection
           against severe dengue disease using a novel peptide set-point vaccine in healthy adults.

        2. To check the absence of an antibody mediated response

      For naNO-DENGUE, a total of 26 eligible participants will be randomized into the following
      groups:

        -  Group 1 (n=13): 10 Low Dose (LD) PepGNP-Dengue (2.5 nmol) + 3 Comparator

        -  Group 2 (n=13): 10 High Dose (HD) PepGNP-Dengue (7.5 nmol) + 3 Comparator, Thus, 20/26
           vaccine vera and 6/26 Comparator controls. Allocations of vaccine vera vs Comparator for
           each group are double-blinded. Each arm will be staggered into a "Pioneer" group (3/13
           participants) followed a week later after a safety review by the remaining 10/13
           "Followers".

      This is the master protocol for a 2-stage study investigating the safety of 2 vaccines from a
      T Cell priming vaccine platform for emerging diseases:

      Stage 1: naNO-DENGUE A Phase-I study of a nanoparticle-based peptide vaccine against Dengue
      (Master protocol) Stage 2: naNO-COVID A Phase-I study of a nanoparticle-based peptide vaccine
      against SARS-CoV2 (Sub-protocol)
    

Intervention name(s): LD vehicle-GNP; LD PepGNP-Dengue; HD vehicle-GNP; HD PepGNP-Dengue
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): Two intradermal injections in the upper arm spaced 21 days apart; Two intradermal injections in the upper arm spaced 21 days apart; Two intradermal injections in the upper arm spaced 21 days apart; Two intradermal injections in the upper arm spaced 21 days apart
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Dengue; peptide vaccine; T-cell; nanoparticle; Dengue vaccine; T cell vaccine