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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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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
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
  • South Australian Health and Medical Research Institute

    Adelaide, South Australia, 5000

    David Lynn, +61 8 8128 4053, david.lynn@sahmri.com

    David Lynn

    Recruiting

Other trials in Australia

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.

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 groups in NCT06148025
Study groupRoleWhat they receive
Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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 vaccineExperimentalRandomised 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.

  1. 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

  2. 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)
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  1. First posted28 Nov 2023
  2. Study start23 Nov 2023
  3. Primary completion1 Oct 2027 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

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)
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.

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.

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