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

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

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

Monash University, The Peter Doherty Institute for Infection and Immunity, University of Sao Paulo, Johns Hopkins Bloomberg School of Public Health

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).

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.

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.

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.

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.

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.

Change over time in the different vaccine groups of titres measured by haemagglutination inhibition assay.

Change in TNF:IL-10 ratio post-vaccination over time as measured by cytokine multiplex assay of anti-CD3 stimulated PBMC.

Change over time in the different vaccine groups of IFN-g levels in supernatants from CD4 T cells cultured with live influenza virus

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

The transcriptome data will be de-identified and deposited in a pubic database. The de-identified microbiome data may well also be made publically available.

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