Influence of BCG on TDaP-IPV Vaccination

Brief Title

Influence of BCG on TDaP-IPV Vaccination

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 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 Phase

Phase 4

Study Type

Interventional

Primary Outcome

Antibody response to TDaP-IPV

Secondary Outcome

 PBMC responses to heterologous antigens

Condition

Whooping Cough

Intervention

BCG vaccine (SSI)

Study Arms / Comparison Groups

 BCG

Description:  Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

75

Start Date

January 2015

Completion Date

April 2017

Primary Completion Date

July 2016

Eligibility 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
      

Gender

Female

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Mihai Netea, Prof. Dr., , 

Location Countries

Netherlands

Location Countries

Netherlands

NCT ID

NCT02771782

Organization ID

BCG-DKTP1

Responsible Party

Sponsor

Study Sponsor

Radboud University Medical Center

Collaborators

 University of Southern Denmark

Study Sponsor

Mihai Netea, Prof. Dr., Principal Investigator, Radboud University Medical Center

Verification Date

April 2016