To evaluate the safety of LFn-p24 administered at three different doses with Alhydrogel given intramuscularly To evaluate immune responses to LFn-p24 with Alhydrogel at three different doses given intramuscularly
The study seeks to enroll healthy, vaccine naïve volunteers, 18 through 45 years old. Recruitment consists of using flyers, newspaper advertising, radio, and direct mailing at local military installations, targeting the general population of the greater Washington D.C. area. The study's primary objective is the safety and tolerability of Lfn-p24 given IM. Volunteers will be screened (visit 1) and enrolled within 2 to 12 weeks prior to the first vaccination. Study volunteers will receive a briefing from the Principal Investigator (PI) or a sub investigator. The briefing is followed by an opportunity for questions from the volunteers. The PI or designee will then review the consent form with potential volunteers (visit 1) and answer any questions. After review, an Informed Consent will be signed and a "Test of Understanding" will be completed by all volunteers, prior to enrollment in the study. A second pre-screening visit (visit 2) will occur 3 - 30 days prior to the first vaccination (visit 3) to confirm eligibility for vaccination. During this visit each volunteer will have an opportunity to ask questions about the study. On the day of vaccination (visits 3, 6, and 10), volunteers will be observed for 30 minutes following injection for acute adverse experiences and will be contacted the day following injection for a brief adverse reaction interview. In addition, volunteers will complete diaries for 7 days following each vaccination and will be evaluated by a clinical investigator if significant symptoms are reported. Adverse effects and laboratory abnormalities will be tabulated. Routine measurements of hematology, serum chemistry, and urinalysis laboratory tests will be performed in subsequent safety and general follow up visits.renee LFn-p24 with Alhydrogel adjuvant will be delivered IM in the deltoid muscle at the intervals shown below. Groups will be enrolled in staggered fashion beginning with the lowest dose group. The subsequent groups receiving higher doses will then be enrolled by the investigator if the second injection of the immediate lower dose is shown to be safe and well tolerated (\< grade II toxicity), after the 2 week post vaccination follow-up visit. IMMUNIZATION SCHEDULE Group I Subjects \*6 0:150µg LFn-p24 Alhydrogel;4th Week:150µg LFn-p24 Alhydrogel; 16th Week:150µg LFn-p24 Alhydrogel; Group II Subjects \*6 0:300µg LFn-p24 Alhydrogel; 4th Week: 300µg LFn-p24 Alhydrogel; 16th Week: 300µg LFn-p24 Alhydrogel; Group III Subjects \*6 0: 450µg LFn-p24 Alhydrogel; 4th Week: 450µg LFn-p24 Alhydrogel; 16th Week: 450µg LFn-p24 Alhydrogel \*Six subjects per group includes 4 vaccines and 2 placebos.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
18
HIV LFn-p24 is a combination of an Anthrax derived polypeptide Lethal factor (LFn), from which the toxin domain has been removed, and the HIV-1 gag p24 protein has been fused to LFn. Lfn-p24 is formulated in liquid form, and vialed at 200 µg/ml and 600 µglml. The product will be administered IM in doses ranging from 150µg to 450µg with Alhydrogel.
Vaccine Clinical Research Center
Rockville, Maryland, United States
Humoral: Responders to ELISA and Western Blot antibodies to HIV-1 subtype B gag p24
An HIV-I enzyme linked immunosorbent assay (ELISA) assay will be performed as designated throughout the course of the protocol during Visits 1 through 15. If the ELISA is reactive it will be repeated and an FDA- approved HIV Western blot will be performed. If the Western blot is positive, HIV molecular diagnostics (Roche Amplicor) will be performed
Time frame: Days 0, 14, 42, 70, 126, 182, 252 and 364
Cellular: Cytotoxic T-lymphocyte (CTL) responses against subtype B gag antigen target expressed in Epstein Barr Virus (EBV) transformed autologous B cell lines.
Cytotoxic T-lymphocyte (CTL) responses against subtype B gag antigen target expressed in Epstein Barr Virus (EBV) transformed autologous B cell lines. Bulk CTL is currently defined to be positive if the HIV-1 antigen expressing targets relative to control have a specific lysis 10%. CD8+ CTL occurs when lytic activity decreases by 50% after removal of CD8 cells, while removal of CD4 cells maintains specific lysis at 5%. An analogous rule is applied for CD4+ CTL
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
IFN-y ELISPOT assay against HIV-gag antigen.
IFN-y ELISPOT assay using a panel of B clade gag peptides. A positive responder will be defined in accordance with other HIV Vaccine Trial Network (HVTN) definitions. For example a positive response may be defined by a significant difference between the number of IFN-g spot forming cell s (SFC)/million peripheral blood mononuclear cells (PBMC) in the presence of HIV gag antigen and no antigen. Other arbitrary definitions may be used.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
IFN- ICS assay against HIV-gag antigen.
For the IFN-gamma intracellular cytokine staining (ICS) assay we will use a panel of B clade gag peptides or other appropriate gag antigens. A positive responder will be defined in accordance with the HIV Vaccine Trial Network (HVTN) definitions or other definitions as appropriate. For example a positive response may be defined as a two-fold difference between the percentage of CD3+CD8+IFN-y+ or CD3+CD4+IFN-y+ T cells in the presence of HIV gag antigen compared with no antigen
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Lymphocyte proliferative responses to HIV-1 subtype B gag
Lymphocyte proliferative responses to HIV- I subtype B gag p24. The data are expressed as a Lymphocyte Stimulation Index (LSI)= (PBMC cpm + antigen/ mitogen) I (PBMC cpm+ medium)\] to define antigen specificity. Individuals are arbitrarily designated as responders non-responders if their LSI is greater than or equal to 5.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Humoral- Binding antibodies to LFn
Expression profile surveillance of 8000 fully annotated genes in peripheral blood mononuclear cells using the Affymetrix Human Focus GeneChip to assess sentinel genes and associated cellular processes that might be correlated with protection by the vaccine.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Neutralizing antibodies to LFn
Expression profile surveillance of 8000 fully annotated genes in peripheral blood mononuclear cells using the Affymetrix Human Focus GeneChip to assess sentinel genes and associated cellular processes that might be correlated with protection by the vaccine.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364
Cellular: Lymphoproliferation to LFn
Expression profile surveillance of 8000 fully annotated genes in peripheral blood mononuclear cells using the Affymetrix Human Focus GeneChip to assess sentinel genes and associated cellular processes that might be correlated with protection by the vaccine.
Time frame: Days 3, 14, 42, 70, 126, 182, 252, and 364