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

Not Applicable

• Conditions: Heterologous Effects of Vaccines
• Interventions: Biological: Seasonal influenza vaccine; Biological: Diphtheria-tetanus-acellular pertussis vaccine

• Registration Number: NCT02765126
• Lead Sponsor: Clifford Craig Medical Research Trust

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.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-03
• Study First Submitted QC: 2016-05-05
• Study First Posted: 2016-05-06
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-25
• Last Update Posted: 2017-07-27
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 450

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Seasonal influenza vaccine	Diphtheria-tetanus-acellular pertussis vaccine administered day 0, followed by seasonal influenza vaccination four weeks later. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week, 4 weeks, 4 weeks + 24 hours, 5 weeks, 8 weeks and 30 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.
Group 2	Diphtheria-tetanus-acellular pertussis vaccine	Seasonal influenza vaccine administered on day 0, to be offered DTP vaccine at week 26. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week 1, 4 weeks and 26 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.
Group 1	Diphtheria-tetanus-acellular pertussis vaccine	Diphtheria-tetanus-acellular pertussis vaccine administered day 0, followed by seasonal influenza vaccination four weeks later. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week, 4 weeks, 4 weeks + 24 hours, 5 weeks, 8 weeks and 30 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.
Group 2	Seasonal influenza vaccine	Seasonal influenza vaccine administered on day 0, to be offered DTP vaccine at week 26. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week 1, 4 weeks and 26 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.
Group 3	Seasonal influenza vaccine	Seasonal influenza vaccine and DTP vaccine administered together on day 0. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week 1, 4 weeks and 26 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.
Group 3	Diphtheria-tetanus-acellular pertussis vaccine	Seasonal influenza vaccine and DTP vaccine administered together on day 0. Blood testing to occur day 0 (prior to vaccine administration), 24 hours, 1 week 1, 4 weeks and 26 weeks. Stool samples to be taken at day 0 and 1 week post-vaccination.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Clifford Craig Foundation; 🇦🇺 Launceston, Tasmania, Australia