This is a phase 1 study, in healthy volunteers who have previously been immunized with bacilli Calmette Guerin (BCG), to evaluate the safety and immune responses that develop in the blood and lungs following the administration by aerosol of a new experimental adenovirus-based vaccine for tuberculosis (TB), Ad5Ag85A.
This is a phase 1, open label study to evaluate the safety and immunogenicity of a single administration of one of two doses of a recombinant replication deficient human adenoviral (Ad5) TB vaccine containing the immunodominant antigen Ag85A delivered to the respiratory tract by aerosol in healthy volunteers with a history of BCG immunization. 28 healthy volunteers will be enrolled. The first cohort (n=8) will receive a lower dose of vaccine using the AeroNeb Solo Vibrating Mesh Nebulizer. For the second cohort (n=20) participants will be randomized to either a higher dose of vaccine by aerosol (n=10) or intramuscular administration (n=10). Cellular immune responses in the lung and peripheral blood will be evaluated
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
36
Aerosol administration of Ad5Ag85A
McMaster University Medical Centre
Hamilton, Ontario, Canada
Number of participants reporting adverse events
Adverse events will be assessed according to the CTCAE Expanded Common Toxicity Criteria at 48-72 hours after vaccination, and at weeks 2, 4, 8, 12, 16 and 24
Time frame: Over 24 weeks
Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol
Change from baseline in the immune responses of specific T-cells in bronchoalveolar lavage \[BAL\] fluid (mucosal) and blood (systemic). Immune responses measured will include interferon Elispot assay, cytokine production and intracellular cytokine staining
Time frame: Two weeks after vaccination
Immunogenicity of one of two doses of Ad5Ag85A administered by aerosol
Time frame: Eight (first cohort) or twelve (second cohort) weeks after vaccination
Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration
Time frame: Two weeks after vaccination
Immunogenicity of inhaled administration of Ad5Ag85A compared with intramuscular administration
Time frame: Twelve weeks after vaccination
Number of participants reporting adverse events with inhaled administration of Ad5Ag85A compared with intramuscular administration
Time frame: Over 24 weeks
Immune responses measured from induced sputum compared with bronchoalveolar lavage
For first cohort of 8 participants only
Time frame: Two weeks after vaccination
immune responses measured from induced sputum compared with bronchoalveolar lavage
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For first cohort of 8 participants only
Time frame: Eight weeks after vaccination
Number of participants developing a positive interferon release assay for TB after vaccination with Ad5Ag85A
For first cohort of 8 patients only
Time frame: At 16 weeks
Number of participants reporting adverse events correlated with level of pre-existing anti-adenoviral antibodies
Time frame: Over 24 weeks
Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies
Time frame: Two weeks after vaccination
Immune response to vaccination correlated with pre-existing anti-adenoviral antibodies
Time frame: Eight weeks after vaccination
Number of participants reporting adverse effects correlated with dose of vaccine received by inhalation
Time frame: Over 24 weeks
Immune response to vaccine correlated with dose of vaccine received by inhalation
Time frame: Two weeks after vaccination
Immune response to vaccine correlated with dose of vaccine received by inhalation
Time frame: Eight or 12 weeks after vaccination