Collection and Storage of Biological Samples Obtained by Leukapheresis for the Future Study of Immune Responses Induced by Two BCG Vaccinations in BCG-naïve Healthy Adults in the US (A-051)
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Tuberculosis
- Sponsor
- Aeras
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Biological samples
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This protocol will use leukapheresis to collect lymphocytes to study immune responses following vaccination with BCG in BCG-naïve participants. These studies will include, but not necessarily be limited to: anti-T-cell and anti-Natural Killer (NK) T-cell responses, anti-lipid responses, and antibody responses to BCG following re-vaccination. These responses will provide a detailed framework characterizing the immune responses that are induced and responses that are not induced in humans by BCG, a partially protective TB vaccine. This framework will allow new hypotheses to be formulated and tested regarding what new and more effective TB vaccines should target for optimal protective immunity.
Detailed Description
This is an open-label protocol in up to 15 healthy adults who are BCG-naïve. All participants will receive a total of two doses of BCG, by intradermal injection, approximately 6 months apart. Participants will be followed by a combination of visits and telephone contacts through Study Day 264. Participants will undergo TST testing 3 months after the second BCG vaccination and QuantiFERON TB Gold in-Tube (QTBGT), or the equivalent, if necessary. Two BCG vaccinations given 6 months apart were chosen for this study to give optimal T cell and antibody responses for future study. Leukapheresis will be conducted prior to the first BCG vaccination and at 56 days after the second BCG vaccination (Hoft, 2002; Brown, 2003; de Valliere, 2005). The final leukapheresis timing was selected based on results from functional biological assays, which suggest analysis of samples at this time point may provide insight into the protective immune responses elicited by BCG, and on results of prior clinical trials describing the peak immune responses to BCG (Hoft, 2002; Brown, 2003; de Valliere, 2005). The study will be conducted at a single site in the US (Saint Louis University \[SLU\]).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Has completed the written informed consent process.
- •Is age ≥18 years and ≤55 years on Study Day
- •Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study.
- •Agrees to avoid elective surgery during the study.
- •Willingness to receive HIV test results.
- •For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 and for the full duration of the study. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide.
- •Has general good health, confirmed by medical history and physical examination.
- •Has not received vaccination or immunotherapy with a BCG product at any time prior to Study Day
- •Body weight of \> 110 pounds
- •Absence of previous risk factors for HIV infection including:
Exclusion Criteria
- •Participants must have none of the following at the time of study entry:
- •Acute illness on Study Day
- •HIV-1/2 positive
- •Oral temperature ≥37.5°C on Study Day
- •Abnormal laboratory values per local laboratory parameters from most recent blood collection prior to Study Day 0 as follows:
- •hemoglobin, hematocrit, absolute neutrophil count, or absolute lymphocyte count below lower limit of normal (LLN)
- •white blood cell count above upper limit of normal (ULN) or below LLN (i.e., must be within normal limits)
- •ALT, AST, GGT, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine \>1.25 times institutional upper limit of normal
- •Calcium not within institutional normal limits
- •Fibrinogen level \<100 mg/dL.
Outcomes
Primary Outcomes
Biological samples
Time Frame: 8 months
Obtain biological samples through leukapheresis and cryopreservation of cells for the future study, by in vitro assay, of immune responses after two doses of BCG in BCG-naïve healthy adults.