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 Information
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
Administrative Informations
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