Testing if BCG (Bacille Calmette-Guérin) Vaccination Can Induce Innate Immune Training in Adult People Above 50 Years of Age in Guinea-Bissau

The propose is to test innate immune training in a pilot study of 40 adults >50 years of age people in Guinea-Bissau. The hypothesis is that BCG vaccination will be associated with increased innate immune training measured as increased cytokine release after in vitro Peripheral Blood Mononuclear Cells (PBMC) stimulation with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae.

Study Overview

• Status: Completed
• Conditions: Innate Immunity; Bacille Calmette-Guérin
• Intervention / Treatment: Biological: Bacille Calmette-Guerin; Biological: BCG solvent

Detailed Description

BCG was developed as a vaccine against tuberculosis (TB), but many studies have now confirmed its ability to induce potent protection against other infectious diseases in children. It has recently been shown that this may be linked to increased response of the innate immune system to several non-specific pathogens after BCG exposure, so called 'innate immune training'. This training ability of BCG has been shown for children and young adults. However, to our knowledge, no studies on the ability of BCG to induce innate immune training in adults >50 years of age have been conducted. Immune training in elderly is of interest since with increasing age, the immune system gets weaker, and responds less adequately to a number of infections, for instance influenza. Thus, if BCG is able to stimulate the innate immune system in mature adults as well, it could potentially reduce the risk of serious infections in elderly.

To investigate whether BCG has innate immune training effects in mature adults, a randomized pilot study of 40 adults >50 years of age in Guinea-Bissau will be conducted. The Bandim Health Project has conducted multiple large-scale RCT's and demographic surveillance. HIV negative adults >50 years of age in a recent HIV survey are eligible for the present study. They will be checked for clinical signs of TB and an HIV test will be preformed before enrolment. Exclusion criteria are BCG vaccination within the last 10 years, illness within the last 14 days, clinical signs of active TB, and/or a positive HIV test. Those who are overtly ill will be treated or referred to hospital if needed. Those with signs of TB will be referred to the TB hospital for further examinations. Those who have become HIV positive since they were tested in the survey will receive immediate counselling and be referred to the HIV clinic.

Participants will be randomized to either BCG vaccination or placebo. To test the innate immune system blood will be withdraw 3 times: before the intervention, 2 weeks and 3 months after the intervention. There is a maximum of 10 ml blood each time, plus 3 ml the first time for the Quantiferon. This is a small volume, with a maximum of 33 ml and should not cause any problems for participants. Quantiferon results will be used as a baseline to test if participants are sensitized to mycobacterium Tuberculosis. In the blood, the innate immune training effects of BCG we will investigated by studying how the immune cells respond when they are stimulated with bacteria or other pathogens, which can cause serious infections. Provided that BCG shows induced innate immune training in adults >50 years of age, a large randomized control trial will follow to see if BCG vaccination reduces the number of acute infections in adults >50 years of age in Guinea-Bissau.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau Codex
    • Bissau, Bissau Codex, Guinea-Bissau, 1004
      • Bandim Health Project

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adults above 50 years of age

Exclusion Criteria:

• Participants who received BCG in the last 10 years will be excluded.
• Adults who were mild to severe ill in the last 2 week will be excluded.
• Adults how have been in contact with the health system (hospital or health center) for the last 14 days will be excluded.
• People that show signs of overt disease will not be enrolled, but treated according to local standards and invited back when better.
• If the person has any sign of TB, they will excluded and be referred to the TB clinic for further investigations and treatment.
• All participants will be tested for HIV. If the test is positive, they will have an opportunity to talk with a psychologist, and we will refer them to the HIV clinic. HIV positive persons will be excluded from the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Intervention arm, these participants will receive BCG vaccination.	Biological: Bacille Calmette-Guerin; Vaccine against tuberculosis; Other Names: BCG
Placebo Comparator: Placebo arm; The placebo arm will receive BCG solvent.	Biological: BCG solvent; Simple solvent; Other Names: Diluent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cytokine level at 2 weeks compared to the baseline	Before intervention and 2 weeks after, blood will be withdrawn and the PBMC will be isolated. In vitro stimulation of the PBMC will be done with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae for 24h and 7 days. After this the cytokine levels will be measured.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cytokine level at 3 months compared to the baseline	Before intervention and 3 months after the intervention, blood will be withdrawn and the PBMC will be isolated. In vitro stimulation of the PBMC will be done with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae for 24h and 7 days. After this the cytokine levels will be measured. The cytokine level 3 months after intervention is the secondary outcome.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in percentage before and after BCG vaccination of a specific marker on a specific gene (e.g. H3K4me3 on TNF (tumor necrosis factor) gene).	Measurement of change in epigenetics after intervention, compared to before intervention.	2 weeks and 3 months after inclusion
Consultation	The amount of consultations in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.	3 months
Medication use	The amount of medication use in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.	3 months

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Collaborators: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): June 15, 2017
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimate): November 2, 2016

Study Record Updates

• Last Update Posted (Actual): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 22, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Non-Specific Effect of Vaccine; Middle aged; Immunity, heterologous
• Other Study ID Numbers: BCGadult

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No