Effects of BCG on Influenza Induced Immune Response

November 9, 2015 updated by: Radboud University Medical Center

The Effects of BCG-vaccination on the Immune Response Induced by Influenza-vaccination in Healthy Volunteers. A Pilot Proof-of-principle Study.

In the present study, the investigators want to investigate whether prior BCG-vaccination improves the efficacy of influenza ("the flu") vaccination in young and/or old healthy volunteers and consequently could protect against influenza virus infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Influenza virus infection leads to millions of cases of severe illnesses worldwide and up to an estimated 500.000 deaths annually. The potential for the sudden emergence of pandemic influenza strains represents an incessant threat on even a larger scale. seasonal influenza vaccination is the backbone of influenza management. However, antibodies generated by vaccination, most often do not effectively neutralize emergent strains due to the high mutation rate of the influenza viral genome. In addition, although vaccination is effective in up to 85% of healthy adults, only 40-60% of the elderly are able to mount an protective antibody response due to an agerelated decline in immune function (so-called immunoscenescence). As a result, the protective effects of influenza vaccination are limited, and strategies to improve host immune defenses against influenza virus infection per se, and following influenza vaccination, are highly warranted.

It is suggested that prior vaccination with Bacille Calmette-Guérin (BCG) could enhance resistance to other infectious diseases in addition to protection to tuberculosis (TBC) and, in mice, protection of prior BCGvaccination against influenza infection was demonstrated long ago. However, only recently substantial evidence for these nonspecific beneficial effects of BCG-vaccination in humans has been provided by several randomized clinical trials. Considering these potentiating effects of BCG-vaccination, it could be a viable strategy to improve efficacy of influenza vaccination, and/or enhance immune defenses against influenza virus infection per se. If so, this would have an enormous impact on clinical practice.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Age ≥18 and ≤35 yrs
  • Male
  • Healthy

Exclusion Criteria:

  • History of influenza vaccination within the year prior to study entry
  • History of BCG vaccination within 5 years prior to study entry
  • History of Mantoux testing within the year prior to study entry
  • Vaccination other than BCG or influenza, within 3 months prior to study or within study period
  • Medical history of any disease associated with immune deficiency
  • Clinically significant acute illness, including infections, within 4 weeks before vaccination
  • Participation in a drug trial or donation of blood 3 months prior to study entry
  • Use of recreational drugs within 21 days prior to experiment day
  • Recent hospital admission or surgery with general anaesthesia (<3 months)
  • Known chronic kidney or liver disease
  • Latent or active tuberculosis infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BCG vaccination
Biological: BCG
Vaccination with the live attenuated BCG vaccine.
Placebo Comparator: NaCl 0.9%
administration of NaCl 0.9%.
Other: Placebo
Administration of 0.9% NaCl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference in influenza antibody titres between BCG-vaccinated subjects and subjects in the control group
Time Frame: Day 14, day 21, day 28, day 42 (±2 days)
Day 14, day 21, day 28, day 42 (±2 days)
Difference in Thrombocyte function between BCG-vaccinated subjects and subjects in the control group
Time Frame: Day 0, day 14, day 21, day 28, day 42 (±2 days)
Day 0, day 14, day 21, day 28, day 42 (±2 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of participants in each group who achieved seroprotection (defined by antibody titre ≥1:40).
Time Frame: day 21, day 28, day 42 (±2 days)
day 21, day 28, day 42 (±2 days)
Proportion of participants in each group who achieved seroconversion (defined by a ≥4-fold rise in antibody titre).
Time Frame: day 21, day 28, day 42 (±2 days)
day 21, day 28, day 42 (±2 days)
IFN-gamma/IL-10 production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time Frame: Day 0, day 14, day 28, day 42 (±2 days)
Day 0, day 14, day 28, day 42 (±2 days)
Production of Type 1 IFNs, IL-17 and IL-22 by leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time Frame: Day 0, day 14, day 28, day 42 (±2 days)
Day 0, day 14, day 28, day 42 (±2 days)
Production of other inflammatory mediators (including TNFα, IL-1β, IFN-gamma, IL-10, IL-17, IL-22) by leukocytes ex vivo stimulated with different not-related stimuli (including m. tuberculosis, s. aureus, c. albicans, and inactivated influenza).
Time Frame: Day 0, day 21, day 28, day 42 (±2 days)
Day 0, day 21, day 28, day 42 (±2 days)
Inflammatory transcriptional pathways (by use of qPCR/microarrays) .
Time Frame: Day 0, day 14, day 28, day 42 (±2 days)
Day 0, day 14, day 28, day 42 (±2 days)
Granzyme B production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time Frame: Day 0, day 14, day 28, day 42 (±2 days)
Day 0, day 14, day 28, day 42 (±2 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Investigators

  • Principal Investigator: Mihai Netea, PhD, Radboud University Nijmegen Medical Centre, The Netherlands

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

March 10, 2014

First Submitted That Met QC Criteria

April 11, 2014

First Posted (Estimate)

April 15, 2014

Study Record Updates

Last Update Posted (Estimate)

November 10, 2015

Last Update Submitted That Met QC Criteria

November 9, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCG_influenza

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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