Tuberculosis
Conditions
Keywords
BCG vaccine, Vitamin D, Cholecalciferol, Tuberculosis
Brief summary
The purpose of this study is to determine whether a single oral dose of vitamin D given to infants prior to Bacille-Calmette-Guerin (BCG) vaccination will enhance the immune response to BCG vaccination.
Detailed description
In 2000, there were an estimated 884,000 cases of tuberculosis (TB) in children with many developing severe, disseminated disease. Widespread immunization with Bacille-Calmette-Guerin (BCG) vaccine has not been effective in preventing primary TB infection or in halting the progression from latent to active disease. Poor vaccine efficacy has prompted investigators to develop novel TB vaccines and to experiment with enhancing the immune response to the current BCG vaccine. Increasing data indicate that children with low vitamin D levels and specific genetic variants that lower functional levels of vitamin D are at increased risk for severe tuberculosis. Elegant studies investigating Mycobacterium tuberculosis (Mtb) infection have shown that mycobacteria are able to reside in endosomes within macrophages by preventing endosome-lysosome fusion; a critical step in autophagy, a cellular process used to recycle cytoplasmic organelles and proteins, and to degrade microbial organisms including Mtb. In-vitro studies have shown that vitamin D increases autophagy and triggers the production of antimicrobial peptides including cathelicidin. This leads to increased intracellular killing of Mtb and increased Mtb antigen presentation to the immune system. Anti-tuberculous vaccines that over-express Mtb antigens generate a stronger immune response than wild type BCG vaccine. The investigators hypothesis is that a single oral dose of vitamin D3 (cholecalciferol) given to infants prior to BCG administration will enhance the immune response to vaccination through improved MHC class I and class II presentation of the vaccine.
Interventions
DIETARY_SUPPLEMENTVitamin D3 (cholecalciferol)
A single oral dose of 50,000 IU of vitamin D3 (cholecalciferol) will be given prior to Bacille-Calmette-Guerin (BCG) vaccination
Sponsors
Thrasher Research Fund
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Days
Healthy volunteers
Yes
Inclusion criteria
* Healthy mothers \> 18 years of age * Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine
Exclusion criteria
* Recent maternal history of tuberculosis (within 1 year) or active tuberculosis * Known maternal human immuno-deficiency virus (HIV) infection * Maternal fever or chorio-amnionitis * Maternal use of vitamin D, steroids or immuno-regulatory medications * Household member with active tuberculosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bacille-Calmette-Guerin (BCG) vaccine efficacy | 2 months | BCG vaccine efficacy will be assessed by measuring the host immune response against BCG at 2 months, 6 months and one year after BCG immunization. A whole blood assay will be used to measure multiple cytokines and mycobacterial growth suppression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels | 2 months | Serum 25 hydroxy (OH) vitamin D levels will be measured prior to vitamin D supplementation and at 2 months, 6 months and one year after BCG immunization. The investigators will also determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect baseline vitamin D levels and alter the response to vitamin D supplementation. |
| Bacille-Calmette-Guerin (BCG) vaccine efficacy | 1 year | The investigators will determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect the response to BCG vaccine in infants receiving either vitamin D or placebo. |
Countries
Mexico
Outcome results
None listed