The purpose of this study is to: 1. Demonstrate the safety of a novel TB vaccine (ID93/GLA-SE) when given to both BCG-vaccinated and BCG-naïve volunteers. 2. Provide preliminary immunogenicity data of this novel TB vaccine (ID93/GLA-SE). This clinical trial will apply an aerosol BCG challenge model involving 48 participants - 24 historically BCG-vaccinated volunteers and 24 BCG-naïve volunteers. Bronchoscopies will be performed 14 days post-challenge to measure BCG recovered from bronchial samples. Blood tests will be taken to look at potential immunological markers of immunity.
Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide. Key research priorities include the development of an effective vaccine. Currently, the only licensed vaccine against TB is BCG (Bacille Calmette-Guérin). This works well against TB in childhood but is often ineffective in adults. Developing a new TB vaccine is difficult, as it is hard to determine which will be effective. In other diseases, e.g. influenza or malaria, it is possible to experimentally-infect volunteers with the disease to see if the proposed vaccine is effective. This is called a "controlled human challenge or infection model" and is possible in easily treatable or self-limiting diseases. This is not possible with TB, where treatments may be harmful and complex. Using BCG, a live attenuated (weakened) strain of the bacteria that do not cause disease in healthy individuals, the investigators have developed a challenge model to mimic TB infection. Mycobacterium tuberculosis, the bacterium that causes TB, infects people by inhalation into the lungs. Therefore, inhaled BCG more closely imitates TB infection than an injection. Previous studies (TB041 and TB043) and a current study (TB044) in our group used aerosol inhaled BCG in both previously BCG-vaccinated and BCG-naïve volunteers to show that aerosolised BCG could be safely employed, and that BCG could be detected in lung washings two weeks after challenge. A novel TB vaccine (ID93/GLA-SE) has recently undergone clinical trials (phase IIa) to show that it can be given safely to healthy people. Its ability to protect people from TB is currently being investigated. The purpose of this study is to show the safety of this approach and provide preliminary immunogenicity data of this novel TB vaccine (ID93/GLA-SE) in both historically BCG-vaccinated and BCG-naïve volunteers, using an aerosol BCG challenge model. It will involve 48 participants; 12 historically BCG-vaccinated and 12 BCG-naïve participants will initially receive 2 injections of the intramuscular ID93/GLA-SE before challenge with aerosol BCG, while a further 24 participants (12 historically BCG vaccinated) will have aerosol BCG challenge alone. Bronchoscopies will be performed 14 days post aerosol BCG challenge to measure BCG recovered from bronchial samples. Blood samples will be taken to look at potential immunological markers of protection.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
48
ID93/GLA-SE is a protein-adjuvant vaccine which has been purposefully designed to elicit a diverse immune response against M.tb bacterial antigens, improve treatment outcomes and prevent TB disease in people already infected with M.tb. ID93/GLA-SE will be administered intramuscularly.
BCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route. For the challenge, aerosol BCG will be administered via nebulizer.
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxfordshire, United Kingdom
Safety of BCG challenge by the aerosol inhaled route in healthy volunteers and recently ID93/GLA-SE-vaccinated adult volunteers.
Safety will be assessed through actively and passively collected data on adverse events, detailed participant symptom profiles, and lung function test results. Adverse events will be collected at each visit and via diary card. Safety blood tests will be performed at baseline, day 14 and day 70. Lung function tests will be performed at day 0 post challenge and day 28, as well as later time points if clinically indicated.
Time frame: Group A and C - up to day 168, Group B and D - up to day 56 (Adverse events are collected throughout the duration of the study. Specific timepoints for blood and lung function tests have been mentioned in the measure description.)
Differences in colony forming units recoverable of ID93/GLA-SE against a controlled human aerosol BCG infection model.
Difference in BCG recovery from bronchoalveolar lavage fluid 2 weeks after BCG aerosol challenge between ID93/GLA-SE and naïve arms, investigated using time to positivity (number of hours or days for the BCG to flag in the mycobacterium growth indicator tube (MGIT)) and mycobacterial speciation. Bronchoscopies will be performed 14 days post-challenge. Respiratory samples will be cultured for BCG.
Time frame: On day 14 post-challenge
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