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

NCT ID: NCT02953327

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-01
• Study Completion Date: 2020-06-15

Brief Summary

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.

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.

Conditions

Innate Immunity; Bacille Calmette-Guérin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Intervention arm

Intervention arm, these participants will receive BCG vaccination.

Group Type: EXPERIMENTAL

Bacille Calmette-Guerin

Intervention Type: BIOLOGICAL

Vaccine against tuberculosis

Placebo arm

The placebo arm will receive BCG solvent.

Group Type: PLACEBO_COMPARATOR

BCG solvent

Intervention Type: BIOLOGICAL

Simple solvent

Interventions

Bacille Calmette-Guerin

Vaccine against tuberculosis

Intervention Type: BIOLOGICAL

BCG solvent

Simple solvent

Intervention Type: BIOLOGICAL

Other Intervention Names

BCG; Diluent

Eligibility Criteria

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Bandim Health Project

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Bandim Health Project

Bissau, Bissau Codex, Guinea-Bissau

Countries

Guinea-Bissau

References

Berendsen MLT, Bles P, de Bree LCJ, Jensen KJ, Jensen CC, Wejse C, Mendes DV, Netea MG, Benn CS. Bacillus Calmette-Guerin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau. Vaccine. 2024 Dec 2;42(26):126439. doi: 10.1016/j.vaccine.2024.126439. Epub 2024 Oct 17.

Reference Type: DERIVED

PMID: 39423450 (View on PubMed)

Other Identifiers

BCGadult

Identifier Type: -

Identifier Source: org_study_id