Mycobacterial antigen complex 85

The study will commence with a dose-escalation and age de-escalation study in healthy adults and adolescents from the previous Entebbe Mother and Baby Study (EMaBS) in Entebbe, Uganda, focusing on ChAdOx1 85A, to provide safety data for ChAdOx1 85A in this population. These measures are not required for MVA85A since this vaccine has been more widely used, including among adolescents in Uganda, and the dose has been standardised. ChAdOx1 85A dose escalation and age de-escalation will be followed by a Phase IIa randomised trial comparing the immunogenicity of ChAdOx1 85A and MVA85A with the immunogenicity of BCG revaccination. ChAdOx1 85A and MVA85A will be administered via the intramuscular route. The target dose for the Phase IIa trial is 2.5x10^10 viral particles (vp) because the lower dose is expected to have lower immunogenicity, based on the Oxford study, TB034. Data from the Oxford study suggest that this dose will be well tolerated. However, if this dose is not tolerated then the lower dose will be used. The dose of MVA85A will be 1 x 10^8 plaque-forming units (pfu) in the groups in which it is given. There will be 6 study groups with 3 to 30 volunteers in each group.
Dose escalation for ChAdOx1 85A in adults Group 1:
The first three adults will receive ChAdOx1 85A at 5 x10^9 vp.
Group 2:
The next three adults will be enrolled after safety data has been reviewed by the trial management team to one week after ChAdOx1 85A vaccination in group 1. These adults will receive ChAdOx1 85A at 2.5 x10^10 vp.
Age de-escalation and dose escalation for ChAdOx1 85A in adolescents Group 3:
The first three adolescents will be enrolled after safety data has been reviewed to one week after ChAdOx1 85A vaccination in group 2. These three adolescents will receive ChAdOx1 85A at 5 x10^9 vp Group 4. The next three adolescents will be enrolled after safety data has been reviewed to one week after ChAdOx1 85A vaccination in group 2. These three adolescents will receive ChAdOx1 85A at 2.5 x10^10 vp.
Randomised comparison of ChAdOx1 85A-MVA85A versus BCG revaccination:
Once safety data has been reviewed for groups 1 to 4 to one week post ChAdOx1 85A vaccination, recruitment to the randomised trial will commence. Sixty adolescents will be randomised, 30 (group 5) to receive ChAdOx1 85A at 2.5 x10^10 vp followed by MVA85A boost and 30 (group 6) to receive BCG revaccination.
BCG will be obtained from the Serum Institute of India, an approved provider for Uganda, and used at the standard dose of 0.1mL. BCG will be given intradermally.

This is a dose escalating and a paired-placebo design study to describe the safety and immunogenicity profile of candidate TB vaccine ChAdOx1 85A given by aerosol inhaled vaccination versus intramuscular (IM) vaccination in adult healthy volunteers.
It is postulated that the aerosol inhaled route is practical and feasible and has an acceptable safety profile, comparable to the systemic safety profile of the IM route of administration of ChAdOx1 85A in adult healthy volunteers, and that the aerosol inhaled route of administration will induce greater mucosal immunity and comparable systemic immunity when compared to the IM (systemic) route of administration in these volunteers.
Volunteers are followed on a regular basis for safety and immunogenicity, with blood analysis for biological safety tests and immune tests.