Vaccine Response ImpairedPhase 4AVIRSNCT06148025
Antibiotics and Vaccine Immune Responses Study
A Phase 4 study testing BCG vaccine, Yellow Fever vaccine and Vancomycin Oral Capsule in people with Vaccine Response Impaired, run by South Australian Health and Medical Research Institute at 1 site in Australia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Vaccine Response Impaired
- What is being tested?
- BCG vaccine, Yellow Fever vaccine and Vancomycin Oral Capsule
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- 1 siteAustralia
- Study dates
- 23 Nov 2023to 1 Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-35 years old
- Provided a signed and dated informed consent form
- BCG naïve (Arm 1) and BCG and YF vaccine naïve (Arm 2)
- Willing to take short antibiotic course
- Willing to undergo a punch biopsy (Arm 1)
- Willing to have up to 7 blood samples and 3 stool samples collected over 5-7 months
- Not pregnant or intending to get pregnant for the duration of the study (a pregnancy test will be offered to females)
Who cannot join
- Previous BCG vaccination
- Previous YF vaccination or YFV infection (only applies to participants included in the Yellow Fever Vaccine challenge sub-study)
- Evidence of TB infection (assessed through a questionnaire - IGRA to confirm if needed)
- People with contraindications for BCG vaccination:
- malignancies involving bone marrow or lymphoid systems, primary or secondary immunodeficiencies, HIV infection
- moderate/severe skin disease including eczema, dermatitis or psoriasis
Show all 19Show fewer
- requiring immunosuppressive drugs or other immune modifying drugs e.g. corticosteroids, non-biological immunosuppressants, biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha)
- People with contraindications to YF vaccination:
- History of thymus disease, including myasthenia gravis, thymoma, thymectomy, DiGeorge syndrome, thymic damage from chemoradiotherapy or graft-versus-host disease
- YF vaccination is contraindicated in immunocompromised individuals, including individuals who have HIV infection, primary immunodeficiencies (including inherited IFNAR1 deficiency), or are taking corticosteroids or other immunosuppressive agents and haematopoietic stem cell transplant recipients
- People who have had a haematopoietic stem cell transplant
- Individuals with history of severe allergic reactions to egg or chicken proteins
- Pregnant or breastfeeding or planning to become pregnant
- History of renal disease/insufficiency
- Tattoo obscuring BCG vaccination site(s)
- Any history of severe allergic reaction or anaphylaxis to vaccination or antibiotics
- People with chronic serious underlying illness
- Have received any prescribed oral or intravenous antibiotic in the 28 days prior to study visits 1 and 4 (including isoniazid, rifampicin, streptomycin and ethambutol as these particular antibiotics have activity against M. bovis)
- Have received any vaccinations in the 28 days prior to study visits 1 and 4
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
South Australian Health and Medical Research Institute
Adelaide, South Australia, 5000
David Lynn, +61 8 8128 4053, david.lynn@sahmri.com
David Lynn
About this study
Official title: A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination
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?
Read the detailed description
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.
- Conditions
- Vaccine Response Impaired
- Being tested
- BCG vaccine, Yellow Fever vaccine, Vancomycin Oral Capsule, Neomycin Oral Product, Metoclopramide (Maxolon)
- Keywords
- Healthy participants, 18-35 years old, BCG vaccine, Yellow Fever vaccine, Antibiotics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccineBiological
0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus
Yellow Fever vaccineBiological
0.5ml injected subcutaneously
Vancomycin Oral CapsuleDrug
Also called Firvanq, Vancocin HCl Pulvules
500mg every 6 hours for 3 days
Neomycin Oral ProductDrug
Also called Neo-Fradin
1000mg every 6 hours for 3 days
Metoclopramide (Maxolon)Drug
10mg every 8 hours
Loperamide HClDrug
2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day
| Study group | Role | What they receive |
|---|---|---|
| Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine | Experimental | Randomised to receive antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later Receives: Biological: BCG vaccine; Drug: Vancomycin Oral Capsule; Drug: Neomycin Oral Product; Drug: Metoclopramide (Maxolon); Drug: Loperamide HCl |
| Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine | Experimental | Randomised to receive no antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later Receives: Biological: BCG vaccine |
| Substudy 1 - BCG vaccine, antibiotics and placebo vaccine | Experimental | Randomised to receive antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later Receives: Biological: BCG vaccine; Drug: Vancomycin Oral Capsule; Drug: Neomycin Oral Product; Drug: Metoclopramide (Maxolon); Drug: Loperamide HCl |
| Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine | Experimental | Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later Receives: Biological: BCG vaccine |
| Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine | Experimental | Randomised to receive antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later Receives: Biological: BCG vaccine; Biological: Yellow Fever vaccine; Drug: Vancomycin Oral Capsule; Drug: Neomycin Oral Product; Drug: Metoclopramide (Maxolon); Drug: Loperamide HCl |
| Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine | Experimental | Randomised to receive no antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later Receives: Biological: BCG vaccine; Biological: Yellow Fever vaccine |
| Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine | Experimental | Randomised to receive antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later Receives: Biological: Yellow Fever vaccine; Drug: Vancomycin Oral Capsule; Drug: Neomycin Oral Product; Drug: Metoclopramide (Maxolon); Drug: Loperamide HCl |
| Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine | Experimental | Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later Receives: Biological: Yellow Fever vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sub-study 1 BCG re-challenge
Mycobacterial load (Colony Forming Units (CFU)/mg tissue) 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)
Measured: 2 weeks post BCG challenge
Sub-study 2 Yellow Fever vaccine
Peak Yellow Fever viremia (viral copies/ml plasma) at day 3-7 post YFV vaccination in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX)
Measured: 3, 5, 7 days post YFV challenge
Secondary outcomes (12)
Sub-study 1 - Bacterial load
Bacterial load (16S rRNA gene copies/g stool) in ABX participants compared to No-ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of BCG challenge
Sub-study 2 - Bacterial load
Bacterial load (16S rRNA gene copies/g stool) in ABX participants compared to No-ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of YFV challenge
Sub-study 1 - Microbiota diversity
Microbiota diversity (Shannon diversity index) in ABX participants compared to No-ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of BCG challenge
Sub-study 2 - Microbiota diversity
Microbiota diversity (Shannon diversity index) in ABX participants compared to No-ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of YFV challenge
Sub-study 1 - Mycobacterial load
Mycobacterial load (CFU/mg tissue) in the skin biopsy site of BCG-vaccinated participants compared to placebo-vaccinated participants
Measured: 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific IFNγ responses
Mycobacterial-specific IFNγ responses (number of spot-forming units) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific CD4+ T cell activation marker responses
Mycobacterial-specific T cell activation-induced marker expression (frequency of OX40+CD137+ CD4+ T cells) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific CD8+ T cell activation marker responses
Mycobacterial-specific T cell activation-induced marker expression (frequency of CD69+CD137+ cells of CD8+ T cells) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 2 - Peak viraemia
Peak viraemia (viral copies/ml plasma) at day 3-7 post YFV challenge in BCG-vaccinated participants compared to placebo-vaccinated participants
Measured: 3, 5 and 7 days post YFV challenge
Sub-study 2 - Heterologous TNFα responses following R848 stimulation
TNFα cytokine production (pg/mL) following stimulation of PBMC with resiquimod (R848) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Sub-study 2 - Heterologous TNFα responses following LPS stimulation
TNFα cytokine production (pg/mL) following stimulation of PBMC with lipopolysaccharide (LPS) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Sub-study 2 - Heterologous TNFα responses following HKCA stimulation
TNFα cytokine production (pg/mL) following stimulation of PBMC with heat-killed Candida albicans (HKCA) in BCG-ABX participants compared to BCG-No ABX participants
Measured: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2023
- Study start23 Nov 2023
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vaccine Response ImpairedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are allocated to Substudy 1 (BCG re-challenge) or Substudy 2 (Yellow Fever vaccine) Participants are randomised to receive * antibiotics or comparator (unblinded) and * BCG vaccine or placebo (blinded) * BCG vaccine or Yellow Fever vaccine (unblinded)
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 348 participants (estimated)
Sponsor and investigators
- Lead sponsor
- South Australian Health and Medical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Adelaide Hospital, Flinders University, University of Sydney, Telethon Kids Institute, Centenary Institute
- Responsible party
- Principal investigator, David Lynn, South Australian Health and Medical Research Institute
- Investigators
- David Lynn, Principal investigator, South Australian Health and Medical Research InstituteSimone Barry, Principal investigator, Royal Adelaide Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06148025
- Sponsor's protocol ID
- 2023/HREC00066
- Acronym
- AVIRS
- Status last verified
- Sep 2026
- First submitted
- 29 Sep 2023
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Non-identifiable individual participant data from the study may be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept SAHMRI's conditions, under a collaborator agreement, for accessing: * Individual participant data that underlie the results reported in our articles after deidentification (text, tables, figures and appendices) * Study protocol, Statistical Analysis Plan, PICF Molecular data generated from this study (i.e. transcriptomic, epigenomic and metagenomic) will be labelled with a unique identification code and stored on an appropriate data repository (e.g. Gene Expression Omnibus, Sequence Read Archive) with demographic information (age and sex). No identifying participant information will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination
- ClinicalTrials.gov ID
- NCT06148025
- Acronym / sponsor ID
- AVIRS / 2023/HREC00066
- Conditions
- Vaccine Response Impaired
- Keywords
- Healthy participants, 18-35 years old, BCG vaccine, Yellow Fever vaccine, Antibiotics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 348 participants (estimated)
- Lead sponsor
- South Australian Health and Medical Research InstituteUniversity, hospital or other
- Collaborators
- Royal Adelaide Hospital, Flinders University, University of Sydney, Telethon Kids Institute, Centenary Institute
- Study start
- 23 Nov 2023 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 28 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
- Model description
- Participants are allocated to Substudy 1 (BCG re-challenge) or Substudy 2 (Yellow Fever vaccine) Participants are randomised to receive * antibiotics or comparator (unblinded) and * BCG vaccine or placebo (blinded) * BCG vaccine or Yellow Fever vaccine (unblinded)
| Arm | Type | Receives |
|---|---|---|
| Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine | Experimental | Biological: BCG vaccine, Drug: Vancomycin Oral Capsule, Drug: Neomycin Oral Product, Drug: Metoclopramide (Maxolon), Drug: Loperamide HClRandomised to receive antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later |
| Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine | Experimental | Biological: BCG vaccineRandomised to receive no antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later |
| Substudy 1 - BCG vaccine, antibiotics and placebo vaccine | Experimental | Biological: BCG vaccine, Drug: Vancomycin Oral Capsule, Drug: Neomycin Oral Product, Drug: Metoclopramide (Maxolon), Drug: Loperamide HClRandomised to receive antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later |
| Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine | Experimental | Biological: BCG vaccineRandomised to receive no antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later |
| Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine | Experimental | Biological: BCG vaccine, Biological: Yellow Fever vaccine, Drug: Vancomycin Oral Capsule, Drug: Neomycin Oral Product, Drug: Metoclopramide (Maxolon), Drug: Loperamide HClRandomised to receive antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later |
| Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine | Experimental | Biological: BCG vaccine, Biological: Yellow Fever vaccineRandomised to receive no antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later |
| Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine | Experimental | Biological: Yellow Fever vaccine, Drug: Vancomycin Oral Capsule, Drug: Neomycin Oral Product, Drug: Metoclopramide (Maxolon), Drug: Loperamide HClRandomised to receive antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later |
| Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine | Experimental | Biological: Yellow Fever vaccineRandomised to receive no antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 18-35 years old
- Provided a signed and dated informed consent form
- BCG naïve (Arm 1) and BCG and YF vaccine naïve (Arm 2)
- Willing to take short antibiotic course
- Willing to undergo a punch biopsy (Arm 1)
Key exclusion criteria (19 listed)
- Previous BCG vaccination
- Previous YF vaccination or YFV infection (only applies to participants included in the Yellow Fever Vaccine challenge sub-study)
- Evidence of TB infection (assessed through a questionnaire - IGRA to confirm if needed)
- People with contraindications for BCG vaccination:
- People with contraindications to YF vaccination:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG vaccine0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus | Biological | Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, antibiotics and placebo vaccine, Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine |
| Yellow Fever vaccine0.5ml injected subcutaneously | Biological | Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine |
| Vancomycin Oral CapsuleAlso: Firvanq, Vancocin HCl Pulvules500mg every 6 hours for 3 days | Drug | Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine |
| Neomycin Oral ProductAlso: Neo-Fradin1000mg every 6 hours for 3 days | Drug | Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine |
| Metoclopramide (Maxolon)10mg every 8 hours | Drug | Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine |
| Loperamide HCl2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day | Drug | Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine, Substudy 1 - BCG vaccine, antibiotics and placebo vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine, Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine |
Primary outcome
Sub-study 1 BCG re-challenge
Time frame: 2 weeks post BCG challenge
Mycobacterial load (Colony Forming Units (CFU)/mg tissue) 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)
Sub-study 2 Yellow Fever vaccine
Time frame: 3, 5, 7 days post YFV challenge
Peak Yellow Fever viremia (viral copies/ml plasma) at day 3-7 post YFV vaccination in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX)
12 secondary outcomes
Sub-study 1 - Bacterial load
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of BCG challenge
Sub-study 2 - Bacterial load
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of YFV challenge
Sub-study 1 - Microbiota diversity
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of BCG challenge
Sub-study 2 - Microbiota diversity
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), Day of vaccination and Day of YFV challenge
Sub-study 1 - Mycobacterial load
Time frame: 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific IFNγ responses
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific CD4+ T cell activation marker responses
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 1 - Mycobacterial-specific CD8+ T cell activation marker responses
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination), 2 weeks post vaccination, Day of BCG challenge and 2 weeks post BCG challenge
Sub-study 2 - Peak viraemia
Time frame: 3, 5 and 7 days post YFV challenge
Sub-study 2 - Heterologous TNFα responses following R848 stimulation
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Sub-study 2 - Heterologous TNFα responses following LPS stimulation
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Sub-study 2 - Heterologous TNFα responses following HKCA stimulation
Time frame: Baseline (1-2 weeks before BCG/placebo vaccination) and Day of YFV challenge
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: Yes. Non-identifiable individual participant data from the study may be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept SAHMRI's conditions, under a collaborator agreement, for accessing: * Individual participant data that underlie the results reported in our articles after deidentification (text, tables, figures and appendices) * Study protocol, Statistical Analysis Plan, PICF Molecular data generated from this study (i.e. transcriptomic, epigenomic and metagenomic) will be labelled with a unique identification code and stored on an appropriate data repository (e.g. Gene Expression Omnibus, Sequence Read Archive) with demographic information (age and sex). No identifying participant information will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Lynn principal investigator
South Australian Health and Medical Research Institute
Simone Barry principal investigator
Royal Adelaide Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing BCG vaccine, Yellow Fever vaccine and Vancomycin Oral Capsule in people with Vaccine Response Impaired, run by South Australian Health and Medical Research Institute at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Lynn (+61 8 8128 4053, david.lynn@sahmri.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sub-study 1 BCG re-challenge (time frame: 2 weeks post BCG challenge). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.