Influence of BCG on TDaP-IPV Vaccination

Whooping Cough Clinical Trial

Official title:

The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02771782
• Other study ID #: BCG-DKTP1
• Status: Active, not recruiting
• Phase: Phase 4
• First received: February 22, 2016
• Last updated: October 12, 2016
• Start date: January 2015
• Est. completion date: April 2017

Study information

• Verified date: April 2016
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: April 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Whooping Cough

Intervention

Biological:
• BCG vaccine (SSI)

• TDaP-IPV vaccine

Locations

Country	Name	City	State
Netherlands	Radbdoudumc	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	University of Southern Denmark

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Leukocyte differential count	Leukocyte differential counts will be performed	1 day,	No
Other	Leukocyte differential count	Leukocyte differential counts will be performed	4 days	No
Other	Leukocyte differential count	CBC parameters will be measured before and after vaccination	2 weeks	No
Other	Leukocyte differential count	Leukocyte differential counts will be performed	3 months	No
Other	Leukocyte differential count	Leukocyte differential counts will be performed	1 year	No
Other	NK cell phenotype	NK cell activation markers will be assessed by FACS	2 weeks	No
Other	NK Cell phenotype	NK cell activation markers will be assessed by FACS	3 months	No
Other	NK cell phenotype	NK cell activation markers will be assessed by FACS	1 year	No
Other	NK cell function	degranulation of NK cells upon stimulation with tumor cells will be assessed	2 weeks	No
Other	NK cell function	degranulation of NK cells upon stimulation with tumor cells will be assessed	3 months	No
Other	NK cell function	degranulation of NK cells upon stimulation with tumor cells will be assessed	1 year	No
Primary	Antibody response to TDaP-IPV	antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.	2 weeks	No
Primary	Antibody response to TDaP-IPV	antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.	3 months	No
Primary	Antibody response to TDaP-IPV	antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.	1 year	No
Primary	T-cell response to TDaP-IPV	T-cell responses will be measured by FACS	2 weeks	No
Primary	T-cell response to TDaP-IPV	T-cell responses will be measured by FACS	3 months	No
Primary	T-cell response to TDaP-IPV	T-cell responses will be measured by FACS	1 year	No
Primary	PBMC cytokine response to pertussis related antigens	IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g	2 weeks	No
Primary	PBMC cytokine response to pertussis related antigens	IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g	3 months	No
Primary	PBMC cytokine response to pertussis related antigens	IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g	1 year	No
Primary	B-cell phenotype analysis	pertussis specific B-cells will be analyzed by FACS	2 weeks	No
Primary	B-cell phenotype analysis	pertussis specific B-cells will be analyzed by FACS	3 months	No
Primary	B-cell phenotype analysis	pertussis specific B-cells will be analyzed by FACS	1 year	No
Secondary	PBMC responses to heterologous antigens	PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured	1 day	No
Secondary	PBMC responses to heterologous antigens	PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured	4 days	No
Secondary	PBMC responses to heterologous antigens	PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured	2 weeks	No
Secondary	PBMC responses to heterologous antigens	PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured	3 months	No
Secondary	PBMC responses to heterologous antigens	PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured	1 year	No
Secondary	Transcriptional profile of PBMCs	Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs	1 day	No
Secondary	Transcriptional profile of PBMCs	Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs	4 days	No
Secondary	Transcriptional profile of PBMCs	Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs	2 weeks	No
Secondary	Transcriptional profile of PBMCs	Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs	3 months	No
Secondary	Epigenetic markers of monocytes	Levels of activating and inhibiting epigenetic marks will be assessed	1 day	No
Secondary	Epigenetic markers of monocytes	Levels of activating and inhibiting epigenetic marks will be assessed	4 days	No
Secondary	Epigenetic markers of monocytes	Levels of activating and inhibiting epigenetic marks will be assessed	2 weeks	No
Secondary	Epigenetic markers of monocytes	Levels of activating and inhibiting epigenetic marks will be assessed	3 months	No