A Phase-I Study of a Nanoparticle-based Peptide Vaccine Against SARS-CoV-2
Condition: Coronavirus; SARS-CoV-2 Infection; COVID-19
MeSH terms: COVID-19; Coronavirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This trial is Stage 2 of a 2-part adaptive trial. The study aims to investigate the safety of
      2 doses of a T-cell priming specific cocktail of Coronaviruses peptides mounted on a gold
      nanoparticle.

      Note: Stage 1 of the 2-part adaptive trial, testing a specifically selected mix of Dengue
      virus peptides, commenced Aug 2021. This is now in follow up (NCT04935801).
    

Detailed description: 
      Despite drastic quarantine measures, SARS-CoV-2 continues to propagate and threaten global
      economies and healthcare systems. There is universal consensus on the need for vaccination to
      protect against complications, reduce viral shedding and therefore prevent severe
      manifestation of disease and reduce hospitalisations.

      Coronavirus harbours the potential to become a seasonal disease. It is moving towards being a
      ''new flu'' with potential perennial circulation and continuously evolving Variants of
      Concern (VOCs), needing diverse vaccines to control it. The Global Vaccine Alliance, GAVI,
      has specifically advocated for vaccine diversity as a means to ensure equality and access as
      well as a means of maximising scalability.

      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
      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. The scale of the COVID-19 pandemic requires multiple vaccine candidates to ensure
           democratic and rapid access to protection by:

             -  Providing a range of vaccine choices tailored to variations in immunological
                profiles across demographics as well as suited to environments with various levels
                of resources (cold chain etc).

             -  Distributing and parallelizing manufacture, to speed up scale, avoid reagent stock
                limitations and dilute monopolies.

        2. The ability for SARS-CoV-2 to mutate, requires multiple vaccine candidates to ensure
           robust and sustainable protection. Vaccines with a range of epitopes and immune targets
           provide immunological diversity and reduce vulnerability to mutant escape.

        3. Nanotechnology fulfils the needs of a COVID vaccine by being a rapidly scalable and
           modular platform.

        4. Humoral immunity may be transient and insufficient against emerging variants of
           SARS-CoV-2.

        5. Cellular immunity against SARS-CoV-2 is lasting and associated with recovery in
           COVID-19.

      The proposed vaccine of this trial specifically seeks to diversify the immunological target
      response by carefully curating an MHC-I binding antigen cocktail from the SARS viruses
      ligandome and loading it onto a robust nanoparticle for controlled release and coupled T-cell
      immunostimulation. It also specifically seeks to avoid generating a humoral response, which
      has the potential to be transient and even detrimental in certain cases.

      For this second stage of the trial, the objectives are are follows:

      Primary:

      To evaluate the safety and reactogenicity of two intradermal injections of two different
      doses of the investigational COVID peptide T-cell inducing vaccine (PepGNP-Covid19)
      administered to healthy volunteers in Switzerland as a:

        1. candidate vaccine for the prevention of COVID-19

        2. proof-of-concept for a rapidly scalable modular peptide vaccine platform.

      Secondary:

        1. To assess the evidence of a CD8 T-cell mediated immune response as a surrogate of
           protection against severe COVID-19 disease using a novel peptide set-point vaccine in
           healthy adults.

        2. To assess the presence of an antibody mediated response.

      For naNO-COVID, a total of 26 eligible participants will be randomised into the following
      groups:

      Group 1 (n=13) 10 low dose (LD) PepGNP-Covid19 (2.5nmol peptide +12.8ug) + 3 Comparator.

      Group 2 (n=13) 10 high dose (HD) PepGNP-Covid19 (7.5nmol + 38.3ug) + 3 Comparator.

      Thus, 20/26 vaccine and 6/26 Comparator controls. Allocations of vaccine vs bpC 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 second stage of a 2-stage study investigating the safety of 2 vaccines from a
      T-cell priming vaccine platform for emerging diseases. (stage 1 = naNO-Dengue, stage 2 =
      naNO-COVID).
    

Intervention name(s): LD Vehicle-GNP; LD PepGNP-Covid19; HD Vehicle-GNP; HD PepGNP-Covid19
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: Coronavirus; SARS-CoV-2; COVID-19; T-cell priming; COVID vaccine; nanoparticle; T-cell vaccine