Overview

This trial is active, not recruiting.

Condition whooping cough
Treatments bcg vaccine (ssi), tdap-ipv vaccine
Phase phase 4
Sponsor Radboud University
Collaborator University of Southern Denmark
Start date January 2015
End date July 2016
Trial size 75 participants
Trial identifier NCT02771782, BCG-DKTP1

Summary

This study has three purposes:

To investigate whether the immune response to pertussis is increased when TDaP-IPV is given together with BCG vaccine, compared to when it is given alone.

To investigate whether BCG vaccination modulates the immune response to non vaccine target antigens (i.e., antigens/pathogens not used in the vaccine itself).

To investigate whether TDaP-IPV vaccination modulates the immune response to non vaccine target antigens.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal
bcg vaccine (ssi)
(Experimental)
Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular
tdap-ipv vaccine
(Experimental)
Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously
bcg vaccine (ssi)
tdap-ipv vaccine

Primary Outcomes

Measure
Antibody response to TDaP-IPV
time frame: 2 weeks
Antibody response to TDaP-IPV
time frame: 3 months
Antibody response to TDaP-IPV
time frame: 1 year
T-cell response to TDaP-IPV
time frame: 2 weeks
T-cell response to TDaP-IPV
time frame: 3 months
T-cell response to TDaP-IPV
time frame: 1 year
PBMC cytokine response to pertussis related antigens
time frame: 2 weeks
PBMC cytokine response to pertussis related antigens
time frame: 3 months
PBMC cytokine response to pertussis related antigens
time frame: 1 year
B-cell phenotype analysis
time frame: 2 weeks
B-cell phenotype analysis
time frame: 3 months
B-cell phenotype analysis
time frame: 1 year

Secondary Outcomes

Measure
PBMC responses to heterologous antigens
time frame: 1 day
PBMC responses to heterologous antigens
time frame: 4 days
PBMC responses to heterologous antigens
time frame: 2 weeks
PBMC responses to heterologous antigens
time frame: 3 months
PBMC responses to heterologous antigens
time frame: 1 year
Transcriptional profile of PBMCs
time frame: 1 day
Transcriptional profile of PBMCs
time frame: 4 days
Transcriptional profile of PBMCs
time frame: 2 weeks
Transcriptional profile of PBMCs
time frame: 3 months
Epigenetic markers of monocytes
time frame: 1 day
Epigenetic markers of monocytes
time frame: 4 days
Epigenetic markers of monocytes
time frame: 2 weeks
Epigenetic markers of monocytes
time frame: 3 months

Eligibility Criteria

Female participants from 18 years up to 55 years old.

Inclusion Criteria: - healthy females Exclusion Criteria: - systemic medication use other than oral contraceptive drugs - history of disease resulting in immunodeficiency - previous vaccination with BCG - pregnancy - allergy to neomycin or polymyxin - known previous allergic reaction to vaccination with diphteria, tetanus, pertussis or polio vaccines - One of following phenomena after previous vaccination with pertussis containing antigens: Fever >40 °C within 48 hours after vaccination, hypotonous-hyporesponsiveness episode within 48 hours after vaccination, convulsions with or without fever within 3 days after vaccination

Additional Information

Official title The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study
Principal investigator Mihai Netea, Prof. Dr.
Description Rationale: The Bacillus Calmette-Guerin (BCG) vaccine not only protects against Mycobacterium tuberculosis, but has also been shown to reduce morbidity and mortality caused by non-related infections. This effect is likely due to non-specific immunomodulatory effects, at least in part on the innate immune system. Additionally, BCG has been shown to improve immunogenicity of other vaccinations. In contrast, whilst the diphtheria-tetanus-pertussis (DTP) combination vaccine protects against infection with Bordetella pertussis, Clostridium tetani and Corynebacterium diphtheria, it has also been associated with increased mortality due to unrelated infections, particularly in girls in high-mortality countries. Although widespread DTP vaccination has initially reduced pertussis mortality, the disease has persisted and recently resurged in a number of countries with highly vaccinated populations, including the Netherlands. This has been partially attributed to the switch from a whole-cell vaccine (which is still being used in low-income countries) to a more defined acellular pertussis vaccine, which only protects for a limited period (5-8 years). Strategies to improve the efficacy of pertussis vaccination are therefore urgently required. As the BCG vaccine has already been used to improve the immunogenicity of other vaccines, the investigators hypothesize that BCG vaccination before or at the same time of DTP vaccination increases the immunogenicity of the DTP vaccine in terms of antibody and T-cell responses to pertussis. Moreover, the investigators aim to assess the effect of DTP vaccination on the known long-term beneficial non-specific effects of BCG on non-mycobacterial infections. Objective: To examine the effect of BCG as an adjuvant on DTP vaccination, and to investigate the non-specific training effects of BCG and DTP, alone and in combination, on the innate immune system. Study population: Healthy adult volunteers. Main study parameters: Comparison of pertussis-specific antibody and T-cell responses, as well as gene transcription between BCG, TDaP-IPV and BCG+TDaP-IPV vaccinated groups. Comparison of cytokine responses to unrelated antigens and/or pathogens before and after BCG, TDaP-IPV or BCG+TDaP-IPV vaccination. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no direct benefit to the study participants but these results will potentially lead to novel strategies to optimize vaccinations. The risks for participants are negligible, with the only expected risks being minor side-effects from vaccination and local hematoma forming at the site of venepuncture. This will be minimized by the performance of these procedures by experienced personnel.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Radboud University.