Heterologous Effects of Vaccines
Conditions
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 description
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.
Interventions
BIOLOGICALSeasonal influenza vaccine
Intramuscular standard seasonal influenza vaccine
Intramuscular DTaP vaccine
Sponsors
Monash University
The Peter Doherty Institute for Infection and Immunity
University of Sao Paulo
Johns Hopkins Bloomberg School of Public Health
Clifford Craig Medical Research Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Two study groups 30-50 years old \>65 years old
Exclusion criteria
* Unwell on day of vaccination * Temperature \>38°C * Active cancer * Active autoimmune disease * Diabetes mellitus * Taking immunosuppressive drugs including steroids * Any vaccination in last 3 months * DT or DTaP vaccination in the last year * Known allergy or contraindication to influenza or DTaP vaccination * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of inflammation reactive TNFR2+ regulatory T cells per mL of blood | 24 hours, 1 week, 4 weeks and 26 weeks | Change over time in different vaccine groups of Tregs measured by flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole human genome transcription profile by next generation sequencing in log2 expression levels | 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 | 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 | 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 | 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 |
Countries
Australia
Contacts
Primary ContactKathryn Ogden, MPH FRACGP
Backup ContactJane Niekamp
Outcome results
None listed