NCT06148025

Antibiotics and Vaccine Immune Responses Study

A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 348 (estimated)
• Sponsor: South Australian Health and Medical Research Institute · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

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?

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

Interventions

Type	Name	Description
BIOLOGICAL	BCG vaccine	0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus
BIOLOGICAL	Yellow Fever vaccine	0.5ml injected subcutaneously
DRUG	Vancomycin Oral Capsule	500mg every 6 hours for 3 days
DRUG	Neomycin Oral Product	1000mg every 6 hours for 3 days
DRUG	Metoclopramide (Maxolon)	10mg every 8 hours
DRUG	Loperamide HCl	2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

Timeline

• Start date: 2023-11-23
• Primary completion: 2027-10-01
• Completion: 2028-10-01
• First posted: 2023-11-28
• Last updated: 2025-12-10

Locations

1 site across 1 country: Australia