AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.
The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations. AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
487
Boro Heath Center
Boro, Kenya
KEMRI/CDC Research and Public Heath Collaboration
Kisumu, Kenya
Siaya District Hospital
Siaya, Kenya
CISM: Centro de Investigacao em Saude de Manhica
Manhiça, Mozambique
Adverse Events Collected Per Subject
Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile
Time frame: Up to 24 months post vaccination
Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects
To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric ICS of CD4 and CD8 T cells producing any of three cytokines (IFN-γ, TNF-α, and/or IL-2) alone or in combination after stimulation with a peptide pool of mycobacterial peptides. Dimethylsulfoxide (DMSO) subtracted responses are presented.
Time frame: 28 days post last vaccination
Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay
To evaluate the immunogenicity of AERAS-402 compared to controls. ELISpot assay of specific T cell responses after stimulation with a peptide pool of mycobacterial peptides. Values presented have been corrected for background readings.
Time frame: 28 days post last vaccination
Antigen-specific Antibody Response - Mean Optical Density (Mean OD)
To evaluate the immunogenicity of AERAS-402 compared to controls by ELISA Assay for Antigen-specific Antibody Response. Median responses of individual Mean OD (absorbance at 450nm) by study group is presented. Higher OD values suggests the presence of antibody to each of the Mtb antigens (Ag85A, Ag85B and TB10.4).
Time frame: 28 day post last vaccination
Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination
To evaluate the proportion of on-study QuantiFERON conversions from negative to positive in infants that received AERAS-402 compared to controls. A QFT value of on \>= 0.35IU/mL was considered positive for this study.
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Univeristy of Cape Town
Cape Town, South Africa
Perinatal HIV Research Unit (PHRU) Chris Hani Baragwanath Hospital
Soweto, South Africa
SATVI: Worcester
Worcester, South Africa
Time frame: up to 24 months post vaccination