Clinical trial NCT02765126: Heterologous Effect of Diptheria, Tetanus, Acellular Pertussis Vaccination on Influenza Challenge in the Elderly
Official title: Clifford Craig Vaccine Trial Centre: Heterologous Effect of Diptheria, Tetanus, Acellular Pertussis Vaccination on Influenza Vaccine Challenge in the Elderly
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heterologous Effects of Vaccines
Lead sponsor: Clifford Craig Medical Research Trust
Sponsor class: OTHER
Collaborators: name: Monash University
name: The Peter Doherty Institute for Infection and Immunity
name: University of Sao Paulo
name: Johns Hopkins Bloomberg School of Public Health
First posted: 2016-05-06
Enrollment: 450
Sex: ALL
Minimum age (years): 30
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of inflammation reactive TNFR2+ regulatory T cells per mL of blood
timeFrame: 24 hours, 1 week, 4 weeks and 26 weeks
Secondary outcomes:
measure: Whole human genome transcription profile by next generation sequencing in log2 expression levels
timeFrame: 24 hours
measure: Influenza-specific antibody titres to seasonal influenza vaccination
timeFrame: 4 weeks and 26 weeks
measure: Pro-inflammatory (TNF) to anti-inflammatory (IL-10) cytokine ratio in stimulated blood in pg/mL
timeFrame: 24 hours, 1 week, 4 weeks and 26 weeks
measure: Influenza-specific IFN-g CD4 T cell responses to seasonal influenza vaccination in pg/mL
timeFrame: 4 weeks and 26 weeks
Other outcomes:
Locations:
city: Launceston
country: Australia
facility: Clifford Craig Foundation
state: Tasmania
Study officials:
affiliation: Clifford Craig Medical Research Trust
name: Katie Flanagan, PhD FRACP
role: PRINCIPAL_INVESTIGATOR
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