Antibiotics and Vaccine Immune Responses Study
AVIRS
A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination
1 other identifier
interventional
348
1 country
1
Brief 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. 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?
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Nov 2023
Longer than P75 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 29, 2023
CompletedStudy Start
First participant enrolled
November 23, 2023
CompletedFirst Posted
Study publicly available on registry
November 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2028
December 10, 2025
May 1, 2025
3.9 years
September 29, 2023
December 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (11)
Sub-study 1 - Bacterial load
5 years
Sub-study 2 - Bacterial load
5 years
Sub-study 1 - Microbiota diversity
5 years
Sub-study 2 - Microbiota diversity
5 years
Sub-study 1 - Mycobacterial load
5 years
- +6 more secondary outcomes
Study Arms (8)
Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised 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
EXPERIMENTALRandomised to receive no antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later
Interventions
0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus
0.5ml injected subcutaneously
500mg every 6 hours for 3 days
1000mg every 6 hours for 3 days
10mg every 8 hours
2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- Previous BCG or YF vaccination
- Previous YF infection
- Evidence of latent TB infection (LTBI) (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
- 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)
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Royal Adelaide Hospitalcollaborator
- Flinders Universitycollaborator
- University of Sydneycollaborator
- Telethon Kids Institutecollaborator
- Centenary Institutecollaborator
- South Australian Health and Medical Research Institutelead
Study Sites (1)
South Australian Health and Medical Research Institute
Adelaide, South Australia, 5000, Australia
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Simone Barry
Royal Adelaide Hospital
- PRINCIPAL INVESTIGATOR
David Lynn
South Australian Health and Medical Research Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Participants and Investigator are blinded to BCG vaccine or placebo.
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director, Computational & Systems Biology Program
Study Record Dates
First Submitted
September 29, 2023
First Posted
November 28, 2023
Study Start
November 23, 2023
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
October 1, 2028
Last Updated
December 10, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- At time of publication. Data will be available indefinitely.
- Access Criteria
- Researchers from a recognised research institution can approach SAHMRI for access of data. The researcher will need to provide evidence that the proposed use of the data has been ethically reviewed and approved by an Institutional Review Board (IRB)/ Human Research Ethics Committee(HREC), and accept SAHMRI's conditions, under a collaborator agreement.
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.