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Influence of BCG on TDaP-IPV Vaccination

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ClinicalTrials.gov Identifier: NCT02771782
Recruitment Status : Unknown
Verified April 2016 by Radboud University.
Recruitment status was:  Active, not recruiting
First Posted : May 13, 2016
Last Update Posted : October 13, 2016
Sponsor:
Collaborator:
University of Southern Denmark
Information provided by (Responsible Party):
Radboud University

Brief 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.


Condition or disease Intervention/treatment Phase
Whooping Cough Biological: BCG vaccine (SSI) Biological: TDaP-IPV vaccine Phase 4

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study
Study Start Date : January 2015
Actual Primary Completion Date : July 2016
Estimated Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Whooping Cough

Arm Intervention/treatment
Experimental: BCG
Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal
Biological: BCG vaccine (SSI)
Experimental: TDaP-IPV
Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular
Biological: TDaP-IPV vaccine
Experimental: BCG+TDaP-IPV
Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously
Biological: BCG vaccine (SSI)
Biological: TDaP-IPV vaccine



Primary Outcome Measures :
  1. Antibody response to TDaP-IPV [ Time Frame: 2 weeks ]
    antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.

  2. Antibody response to TDaP-IPV [ Time Frame: 3 months ]
    antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.

  3. Antibody response to TDaP-IPV [ Time Frame: 1 year ]
    antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.

  4. T-cell response to TDaP-IPV [ Time Frame: 2 weeks ]
    T-cell responses will be measured by FACS

  5. T-cell response to TDaP-IPV [ Time Frame: 3 months ]
    T-cell responses will be measured by FACS

  6. T-cell response to TDaP-IPV [ Time Frame: 1 year ]
    T-cell responses will be measured by FACS

  7. PBMC cytokine response to pertussis related antigens [ Time Frame: 2 weeks ]
    IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g

  8. PBMC cytokine response to pertussis related antigens [ Time Frame: 3 months ]
    IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g

  9. PBMC cytokine response to pertussis related antigens [ Time Frame: 1 year ]
    IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g

  10. B-cell phenotype analysis [ Time Frame: 2 weeks ]
    pertussis specific B-cells will be analyzed by FACS

  11. B-cell phenotype analysis [ Time Frame: 3 months ]
    pertussis specific B-cells will be analyzed by FACS

  12. B-cell phenotype analysis [ Time Frame: 1 year ]
    pertussis specific B-cells will be analyzed by FACS


Secondary Outcome Measures :
  1. PBMC responses to heterologous antigens [ Time Frame: 1 day ]
    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. PBMC responses to heterologous antigens [ Time Frame: 4 days ]
    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. PBMC responses to heterologous antigens [ Time Frame: 2 weeks ]
    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. PBMC responses to heterologous antigens [ Time Frame: 3 months ]
    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

  5. PBMC responses to heterologous antigens [ Time Frame: 1 year ]
    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

  6. Transcriptional profile of PBMCs [ Time Frame: 1 day ]
    Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs

  7. Transcriptional profile of PBMCs [ Time Frame: 4 days ]
    Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs

  8. Transcriptional profile of PBMCs [ Time Frame: 2 weeks ]
    Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs

  9. Transcriptional profile of PBMCs [ Time Frame: 3 months ]
    Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs

  10. Epigenetic markers of monocytes [ Time Frame: 1 day ]
    Levels of activating and inhibiting epigenetic marks will be assessed

  11. Epigenetic markers of monocytes [ Time Frame: 4 days ]
    Levels of activating and inhibiting epigenetic marks will be assessed

  12. Epigenetic markers of monocytes [ Time Frame: 2 weeks ]
    Levels of activating and inhibiting epigenetic marks will be assessed

  13. Epigenetic markers of monocytes [ Time Frame: 3 months ]
    Levels of activating and inhibiting epigenetic marks will be assessed


Other Outcome Measures:
  1. Leukocyte differential count [ Time Frame: 1 day, ]
    Leukocyte differential counts will be performed

  2. Leukocyte differential count [ Time Frame: 4 days ]
    Leukocyte differential counts will be performed

  3. Leukocyte differential count [ Time Frame: 2 weeks ]
    CBC parameters will be measured before and after vaccination

  4. Leukocyte differential count [ Time Frame: 3 months ]
    Leukocyte differential counts will be performed

  5. Leukocyte differential count [ Time Frame: 1 year ]
    Leukocyte differential counts will be performed

  6. NK cell phenotype [ Time Frame: 2 weeks ]
    NK cell activation markers will be assessed by FACS

  7. NK Cell phenotype [ Time Frame: 3 months ]
    NK cell activation markers will be assessed by FACS

  8. NK cell phenotype [ Time Frame: 1 year ]
    NK cell activation markers will be assessed by FACS

  9. NK cell function [ Time Frame: 2 weeks ]
    degranulation of NK cells upon stimulation with tumor cells will be assessed

  10. NK cell function [ Time Frame: 3 months ]
    degranulation of NK cells upon stimulation with tumor cells will be assessed

  11. NK cell function [ Time Frame: 1 year ]
    degranulation of NK cells upon stimulation with tumor cells will be assessed



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02771782


Locations
Netherlands
Radbdoudumc
Nijmegen, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
University of Southern Denmark
Investigators
Principal Investigator: Mihai Netea, Prof. Dr. Radboud University

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02771782     History of Changes
Other Study ID Numbers: BCG-DKTP1
First Posted: May 13, 2016    Key Record Dates
Last Update Posted: October 13, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Radboud University:
BCG
TDaP-IPV
DPT Vaccine

Additional relevant MeSH terms:
Whooping Cough
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases
Vaccines
BCG Vaccine
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic