RecruitingPhase 4NCT06148025

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


Sponsor

South Australian Health and Medical Research Institute

Enrollment

348 participants

Start Date

Nov 23, 2023

Study Type

INTERVENTIONAL

Conditions

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?


Eligibility

Min Age: 18 YearsMax Age: 35 Years

Inclusion Criteria7

  • 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)

Exclusion Criteria18

  • 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)
  • 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)

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Interventions

BIOLOGICALBCG vaccine

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

BIOLOGICALYellow Fever vaccine

0.5ml injected subcutaneously

DRUGVancomycin Oral Capsule

500mg every 6 hours for 3 days

DRUGNeomycin Oral Product

1000mg every 6 hours for 3 days

DRUGMetoclopramide (Maxolon)

10mg every 8 hours

DRUGLoperamide 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


Locations(1)

South Australian Health and Medical Research Institute

Adelaide, South Australia, Australia

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NCT06148025


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