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Antibiotics and Vaccine Immune Responses Study
The goal of this clinical trial is to examine immune responses to the BCG vaccine in healthy adults who have, or who have not, taken antibiotics to deplete their gut bacteria prior to vaccination. The main question it aims to answer is: does depletion of the gut microbiota lead to impaired BCG-induced protection against specific and non-specific to challenges to the immune system?.
Study details:
The study is divided into two sub-studies. The first sub-study (BCG re-challenge) is an experimental medicine study in 168 healthy participants to determine if depletion of the gut microbiota leads to impaired BCG-induced protection against a subsequent Mycobacterium bovis BCG intradermal challenge. The second sub-study (Yellow Fever vaccine) has a very similar experimental design to the first but will determine if depletion of the gut microbiota leads to impaired BCG-induced protection against other infections.
To assess this, participants in this sub-study (n=180) will be re-challenged after 3 months with a live attenuated viral vaccine, the Yellow Fever vaccine, which induces a mild viremia. In both sub-studies, participants will initially be randomised to receive a 3 day course of antibiotics or none (comparator group). The two groups in each sub-study will be randomised again to receive either BCG vaccine or 0.
9% NaCl placebo injection in the left arm. BCG re-challenge sub-study (Sub-study 1): Six months following randomisation, all participants will receive a BCG vaccine challenge in the right arm. A punch skin biopsy will be taken of this challenge site 2 weeks after the challenge to assess M.
bovis BCG bacterial load in the skin. Yellow Fever vaccine sub-study (Sub-study 2): Three months following randomisation, all participants will receive a Yellow Fever vaccine challenge in the right arm. Blood samples will be collected from Yellow Fever vaccinated participants at day 3, 5 and 7 following Yellow Fever vaccine challenge to quantify Yellow Fever viral load in blood.
All participants in both sub-studies will have blood samples collected at randomisation, before each vaccination, 2 weeks after each BCG vaccination and in the Yellow Fever vaccine sub-study at day 3, 5 and 7 following Yellow Fever vaccination. Stool samples will be collected prior to randomisation, and prior to each vaccination.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : Yes
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-11-23
Primary completion: 2027-10-01
Study completion finish: 2028-10-01
Study type
BASIC_SCIENCE
Phase
PHASE4
Trial ID
NCT06148025
Intervention or treatment
BIOLOGICAL: BCG vaccine
BIOLOGICAL: Yellow Fever vaccine
DRUG: Vancomycin Oral Capsule
DRUG: Neomycin Oral Product
Conditions
- • Vaccine Response Impaired
Find a site
Closest Location:
South Australian Health and Medical Research Institute
Research sites nearby
Select from list below to view details:
South Australian Health and Medical Research Institute
Adelaide, South Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 1 - BCG vaccine, antibiotics and placebo vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine
| BIOLOGICAL: BCG vaccine
|
EXPERIMENTAL: Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine
| BIOLOGICAL: Yellow Fever vaccine
|
EXPERIMENTAL: Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine
| BIOLOGICAL: Yellow Fever vaccine
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Sub-study 1 BCG re-challenge | Mycobacterial load (Colony Forming Units (CFU)) in the skin biopsy site in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX) | 5 years |
Sub-study 2 Yellow Fever vaccine | Yellow Fever viremia (viral copies/ml blood) at D3-7 post YF vaccination in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX) | 5 years |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Sub-study 1 - Bacterial load | Day 0 bacterial load (16S copies/g stool) in all ABX participants vs No-ABX participants | 5 years |
Sub-study 2 - Bacterial load | Day 0 bacterial load (16S copies/g stool) in all ABX participants vs No-ABX participants | 5 years |
Sub-study 1 - Microbiota diversity | Day 0 microbiota diversity (Shannon diversity index) in all ABX participants vs No-ABX participants | 5 years |
Sub-study 2 - Microbiota diversity | Day 0 microbiota diversity (Shannon diversity index) in all ABX participants vs No-ABX participants | 5 years |
Sub-study 1 - Mycobacterial load | Mycobacterial load (CFU) in the skin biopsy site in BCG-vaccinated participants compared to placebo-vaccinated participants | 5 years |
Sub-study 1 - Mycobacterial IFNγ responses | IFNγ production in pg/mL following stimulation of PBMC with mycobacteria in BCG-ABX participants versus BCG-No ABX participants | 5 years |
Sub-study 1 - Mycobacterial T cell activation marker responses | % of CD69+CD137+ CD4 T cells following stimulation of PBMC with mycobacteria in BCG-ABX participants versus BCG-No ABX participants | 5 years |
Sub-study 2 - Peak viraemia | Peak viraemia (viral copies/ml blood) at D3-7 post YF vaccination in BCG-vaccinated participants compared to placebo-vaccinated participants | 5 years |
Sub-study 2 - Heterologous TNFα responses following R848 stimulation | D90 PBMC TNFα responses (pg/mL) following in vitro stimulation with viral ligand R848 in BCG-ABX participants versus BCG-No ABX participants | 5 years |
Sub-study 2 - Heterologous TNFα responses following LPS stimulation | D90 PBMC TNFα responses (pg/mL) following in vitro stimulation with bacterial ligand LPS in BCG-ABX participants versus BCG-No ABX participants | 5 years |
Sub-study 2 - Heterologous TNFα responses following fungal stimulation | D90 PBMC TNFα responses (pg/mL) following in vitro stimulation with fungal ligand heat-killed C. albicans in BCG-ABX participants versus BCG-No ABX participant | 5 years |
Frequently Asked Questions
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