Clinical Trial: Influence of BCG on TDaP-IPV Vaccination

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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.


Detailed Summary:

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
Sponsor: Radboud University

Current Primary Outcome:

  • 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.
  • 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.
  • 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.
  • T-cell response to TDaP-IPV [ Time Frame: 2 weeks ]
    T-cell responses will be measured by FACS
  • T-cell response to TDaP-IPV [ Time Frame: 3 months ]
    T-cell responses will be measured by FACS
  • T-cell response to TDaP-IPV [ Time Frame: 1 year ]
    T-cell responses will be measured by FACS
  • PBMC cytokine response to pertussis related antigens [ Time Frame: 2 weeks ]
    IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
  • PBMC cytokine response to pertussis related antigens [ Time Frame: 3 months ]
    IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
  • PBMC cytokine response to pertussis related antigens [ Time Frame: 1 year ]
    IL-6, TNF,

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • 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
    • 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
    • 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
    • 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
    • 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
    • Transcriptional profile of PBMCs [ Time Frame: 1 day ]
      Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
    • Transcriptional profile of PBMCs [ Time Frame: 4 days ]
      Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
    • Transcriptional profile of PBMCs [ Time Frame: 2 weeks ]
      Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
    • Transcriptional profile of PBMCs [ Time Frame: 3 months ]
      Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
    • Epigenetic markers of monocytes [ Time Frame: 1 day ]
      Levels of activating and inhibiting epigenetic marks will be assessed
    • Epigenetic markers of monocytes [ Time Frame: 4 days ]
      Levels of activating and inhibiting epigenetic marks will be assessed
    • Epigenetic markers of monocytes [ Time Frame: 2 weeks ]
      Levels of activating and inhibiting epigenetic marks will be assessed
    • Epigenetic markers of monocytes [ Time Frame: 3 months ]
      Levels of activating and inhibiting epigenetic marks will be assessed


    Original Secondary Outcome: Same as current

    Information By: Radboud University

    Dates:
    Date Received: February 22, 2016
    Date Started: January 2015
    Date Completion: April 2017
    Last Updated: October 12, 2016
    Last Verified: April 2016