The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses

Not Applicable

Completed

• Conditions: Tetanus; Rotavirus Infections; Reaction - Vaccine Nos; Intestinal Bacteria Flora Disturbance; Streptococcal Pneumonia
• Interventions: Biological: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine

• Registration Number: NCT02538211
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

The purpose of this study is to evaluate if the intestinal microbiota influences rotavirus vaccine immune responses in healthy adult volunteers.

Detailed Description

This study will alter the intestinal microbiota in healthy adults using antibiotics and subsequently measure immune reactions to the rotavirus vaccine (Rotarix), the tetanus vaccine and the pneumococcal vaccine (Pneumo23).

Study Timeline

• Study First Submitted: 2015-08-27
• Study Start: 2015-09
• Study First Submitted QC: 2015-09-01
• Study First Posted: 2015-09-02
• Primary Completion: 2017-01
• Study Completion: 2017-02
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-24
• Last Update Posted: 2017-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 63

Inclusion Criteria

• Healthy, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to starting antibiotics (day -98). A subject with a clinical abnormality or laboratory parameter outside the reference range may be included if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
• Male between 18 and 35 years of age, inclusive at the time of signing the informed consent
• Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form
• Normal defecation pattern (defined as ≤3x/ day and ≥3x/week)

Exclusion Criteria

• Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavorable for enrollment, including inflammatory diseases.
• Subject with any history of immunodeficiency
• Subjects with a history of any type of malignancy
• Subject with a history of thrombocytopenia or bleeding disorder
• Subject has a past or current gastrointestinal disease which may influence the gut microbiota
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• History of alcoholism and/or drinking more than an average of 5 units of alcohol per day
• The subject has received an investigational product within three months of day 0 of the current study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Control group - subjects will receive no antibiotics followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine
Broad-spectrum antibiotics	Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Subjects will receive 7 days of pre-treatment (days -9 to -3) with: * Ciprofloxacin 500mg 2dd1 * Vancomycin 250mg 3dd2 * Metronidazole 500mg 3dd1 followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine
Narrow-spectrum antibiotics	Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine	Subjects will receive 7 days of pre-treatment (days -9 to -3) with: • Vancomycine 250mg 3dd2 followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine

Primary Outcome Measures

Name	Time	Method
Height of serum anti-rotavirus Immunoglobulin A (IgA) response	28 days post-vaccination	Geometric Mean Concentration (GMC)

Secondary Outcome Measures

Name	Time	Method
Time to positivity for serum anti-rotavirus Immunoglobulin A (IgA) and G (IgG) response	day 0 through day 28 post vaccination	(days)
Change in pre and post-vaccination anti-rotavirus (anti-RV) serum neutralizing antibodies measured by Geometric Mean Concentration (GMC)	28 days post-vaccination
Change in pre and post-vaccination anti-RV serum IgG response measured by Geometric Mean Concentration (GMC)	day 0 through day 28 post vaccination
Change in serum tetanus toxoid IgG response, measured as pre and post vaccination titer (international units/mL) ratio	day 0 through day 28 post vaccination
Change in serum pneumococcal poly-saccharide-specific IgG for all vaccine strains , measure in pre and post vaccination titer (micrograms/mL) ratio	day 0 through day 28 post vaccination
Composition of the fecal micro biome before and after antibiotics and between groups measured by the HITChip and bacterial 16S rRNA sequencing	day -9 and day 0 pre vaccination

Trial Locations

Locations (1)

Academic Medical Center; 🇳🇱 Amsterdam, Noord-Holland, Netherlands