Clinical Trial: Heterologous Effect of Diptheria, Tetanus, Acellular Pertussis Vaccination on Influenza Challenge in the Elderly

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Clifford Craig Vaccine Trial Centre: Heterologous Effect of Diptheria, Tetanus, Acellular Pertussis Vaccination on Influenza Vaccine Challenge in the Elderly

Brief Summary: Vaccines can have non-targeted or heterologous (also called non-specific) immunological effects on the immune system i.e. effects other than inducing an immune response against the disease targeted by the vaccine. This trial aims to evaluate the non-specific immunological effects of two vaccines - diphtheria-tetanus-acellular pertussis (DTP) vaccine and seasonal influenza vaccine - in a cohort of elderly humans (>65 years of age) and healthy adult control subjects (30-50 years).

Detailed Summary:

This prospective randomised study aims to investigate the heterologous immunological effects of DTP and seasonal influenza (Flu) vaccination in an elderly Tasmanian population and healthy adults. The study will assess whether prior or concurrent administration of DTP with seasonal Flu vaccination affects generalised inflammation / immune homeostasis and gene expression, with a particular focus of inflammation reactive cells. It will also analyse for effects of DTP on the induction of vaccine-specific immunity to seasonal influenza vaccination (antibodies and cellular). Volunteers will be randomised to one of three vaccine groups and serial blood samples taken for immunological assays for up to 30 weeks.

The study is exploratory and will investigate vaccine effects on multiple immune parameters.


Sponsor: Clifford Craig Medical Research Trust

Current Primary Outcome: Number of inflammation reactive TNFR2+ regulatory T cells per mL of blood [ Time Frame: 24 hours, 1 week, 4 weeks and 26 weeks ]

Change over time in different vaccine groups of Tregs measured by flow cytometry.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Whole human genome transcription profile by next generation sequencing in log2 expression levels [ Time Frame: 24 hours ]
    Differential gene expression 24 hours after vaccination compared to baseline, and vaccine groups compared to see which genes / pathways are affected. Differential transcription determined for each gene, then analysed using modular analysis tools to determine vaccine effects.
  • Influenza-specific antibody titres to seasonal influenza vaccination [ Time Frame: 4 weeks and 26 weeks ]
    Change over time in the different vaccine groups of titres measured by haemagglutination inhibition assay.
  • Pro-inflammatory (TNF) to anti-inflammatory (IL-10) cytokine ratio in stimulated blood in pg/mL [ Time Frame: 24 hours, 1 week, 4 weeks and 26 weeks ]
    Change in TNF:IL-10 ratio post-vaccination over time as measured by cytokine multiplex assay of anti-CD3 stimulated PBMC.
  • Influenza-specific IFN-g CD4 T cell responses to seasonal influenza vaccination in pg/mL [ Time Frame: 4 weeks and 26 weeks ]
    Change over time in the different vaccine groups of IFN-g levels in supernatants from CD4 T cells cultured with live influenza virus


Original Secondary Outcome: Same as current

Information By: Clifford Craig Medical Research Trust

Dates:
Date Received: May 3, 2016
Date Started: May 2016
Date Completion: December 2019
Last Updated: May 5, 2016
Last Verified: May 2016