Influence of BCG on TDaP-IPV Vaccination
- Conditions
- Whooping Cough
- Interventions
- Biological: TDaP-IPV vaccineBiological: BCG vaccine (SSI)
- Registration Number
- NCT02771782
- Lead Sponsor
- Radboud University Medical Center
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 75
- healthy females
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TDaP-IPV TDaP-IPV vaccine Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular BCG+TDaP-IPV TDaP-IPV vaccine Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously BCG BCG vaccine (SSI) Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal BCG+TDaP-IPV BCG vaccine (SSI) Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously
- Primary Outcome Measures
Name Time Method T-cell response to TDaP-IPV 1 year T-cell responses will be measured by FACS
PBMC cytokine response to pertussis related antigens 1 year IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
B-cell phenotype analysis 1 year pertussis specific B-cells will be analyzed by FACS
Antibody response to TDaP-IPV 1 year antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
- Secondary Outcome Measures
Name Time Method PBMC responses to heterologous antigens 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 3 months Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
Epigenetic markers of monocytes 3 months Levels of activating and inhibiting epigenetic marks will be assessed
Trial Locations
- Locations (1)
Radbdoudumc
🇳🇱Nijmegen, Netherlands