Influence of BCG on TDaP-IPV Vaccination

NCT ID: NCT02771782

Last Updated: 2016-10-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2017-04-30

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.

Conditions

Whooping Cough

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

BCG

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

Group Type: EXPERIMENTAL

BCG vaccine (SSI)

Intervention Type: BIOLOGICAL

TDaP-IPV

Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular

Group Type: EXPERIMENTAL

TDaP-IPV vaccine

Intervention Type: BIOLOGICAL

BCG+TDaP-IPV

Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously

Group Type: EXPERIMENTAL

BCG vaccine (SSI)

Intervention Type: BIOLOGICAL

TDaP-IPV vaccine

Intervention Type: BIOLOGICAL

Interventions

BCG vaccine (SSI)

Intervention Type: BIOLOGICAL

TDaP-IPV vaccine

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Southern Denmark

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mihai Netea, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radbdoudumc

Nijmegen, , Netherlands

Countries

Netherlands

References

Blok BA, de Bree LCJ, Diavatopoulos DA, Langereis JD, Joosten LAB, Aaby P, van Crevel R, Benn CS, Netea MG. Interacting, Nonspecific, Immunological Effects of Bacille Calmette-Guerin and Tetanus-diphtheria-pertussis Inactivated Polio Vaccinations: An Explorative, Randomized Trial. Clin Infect Dis. 2020 Jan 16;70(3):455-463. doi: 10.1093/cid/ciz246.

Reference Type: DERIVED

PMID: 30919883 (View on PubMed)

Other Identifiers

BCG-DKTP1

Identifier Type: -

Identifier Source: org_study_id