H5N1 Vaccination With and Without AS03: Systems Biology Analysis
Condition: Influenza
MeSH terms: Influenza, Human; Influenza in Birds
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single center, randomized, double-blinded, controlled, Phase I, small targeted
      prospective study in healthy male and non-pregnant female subjects, 18 to 49 years old,
      inclusive, designed to determine the safety, reactogenicity, and immunogenicity of an
      intramuscular subvirion inactivated monovalent influenza A/H5N1 (HA of A/Indonesia/05/2005)
      virus vaccine manufactured by Sanofi Pasteur administered at 3.75 mcg per dose given with or
      without AS03 adjuvant manufactured by GSK. In the study, each subject will receive two doses
      administered 28 days apart. This study will use a systems biology approach to assess the
      human early gene and protein signatures expressed at Days 1, 3, 7, and 28 after the first
      vaccination. The systems data will be integrated with immunogenicity and reactogenicity data
      to develop a systems model of the human immune response to A/H5N1 vaccine with or without
      AS03 adjuvant.
    

Detailed description: 
      The long term goals of this project are to identify RNA or protein biomarkers within 1 to 7
      days after vaccination in peripheral blood that will predict a successful immune response and
      protection against disease. Adjuvants are used to boost the response of vaccines by
      stimulating the innate immune response. However, the exact mechanism and safety of adjuvants
      is still debated. Systems biology is the study of complex biological processes as integrated
      systems with many interacting components. The goal of systems biology is to make biology more
      predictive. This proposal will use a systems biology approach to identify successful
      immunization biomarkers. The study will use fresh blood samples and patient data collected in
      the proposed VTEU-funded study. At selected time points, volunteers' blood samples will be
      collected and immediately processed. Using these specimens, we will identify and quantify
      changes in the whole transcriptome and proteome of the major immune cells to identify and
      quantify changes in gene expression. We will integrate the changes in gene expression with
      the changes in the immune cells response. We will use mathematical modeling of the
      accumulated data to identify RNA or protein biomarkers that significantly correlate with the
      observed serum hemagglutination inhibition assay (HAI) response,cytokine/chemokine response,
      and cell mediated immunity (CMI) responses. Ultimately, the predictive biomarkers will be the
      foundation for a simple, rapid, inexpensive test to quickly show protection against a
      pathogen or foreign agent after vaccination. This is a single center, randomized,
      double-blinded, controlled, Phase I, small targeted prospective study in healthy male and
      non-pregnant female subjects, 18 to 49 years old, inclusive, designed to determine the
      safety, reactogenicity, and immunogenicity of an intramuscular subvirion inactivated
      monovalent influenza A/H5N1 (HA of A/Indonesia/05/2005) virus vaccine manufactured by Sanofi
      Pasteur administered at 3.75 mcg per dose given with or without AS03 adjuvant manufactured by
      GSK. In the study, each subject will receive two doses administered 28 days apart.
    

Intervention name(s): ASO3 Adjuvant; Influenza A/H5N1 Vaccine
Intervention type(s): Drug; Biological
Intervention description(s): 3.75 mcg of H5N1 hemagglutinin plus AS03, will be administered in 2 doses 28 days apart.; 3.75 mcg of H5N1 hemagglutinin plus AS03 or 3.75 mcg of H5N1 hemagglutinin alone will be administered in two doses 28 days apart.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: influenza, vaccine, H5N1, monovalent, adjuvant, ASO3