The aim is to define the immunogenicity of the candidate vaccine in humans. Its evaluation should be consistent with the hypothetical immunological mechanisms by which the vaccine is assumed to confer protection against TB infection and/ or disease. Relevant immunological parameters should be defined accordingly and suitable assays developed and validated as the clinical plan progresses. In addition, the thorough analysis of the immunogenicity of a vaccine candidate is an important opportunity for the identification of correlates of protection in TB.
Immunological assays to characterise the immunogenicity profile of the candidate vaccine should be developed, optimised for clinical use, and qualified prior to FIH studies.
Immunogenicity data of the Phase 1 and other Phase 1b studies will be analysed to characterise immunogenicity using primary and exploratory endpoints. The elicited immune responses must provide evidence that the candidate induces vaccine antigen(s)-specific immune responses and an evaluation must be made of whether these responses are sufficient to progress development of the candidate vaccine. In addition to safety, immunogenicity will guide the selection of the dose(s) to be further evaluated in Phase 2a study(ies).
Wherever possible a biomarker plan must be prepared prior to embarking on clinical efficacy studies: plans should be made for samples to be collected and bio-banked for future correlates analyses – these samples will be vital for the potential discovery of correlates of risk and/ or protection.
Safe and well-tolerated dose(s) providing the most robust immune response, after evaluation of the dose response pattern, should be selected from the doses evaluated in Phase 2a and in pre-proof of concept study eg POI for further study in Phase 2b. Immunogenicity data from earlier studies should be evaluated to determine if additional assays should be considered for evaluation of immune response in Phase 2a.
Immunological assays should be validated prior to the Phase 2b study.
Biomarker studies should be designed prior to the onset of Phase 2b clinical efficacy studies.
If the candidate vaccine is likely to be administered at or around the time of other vaccines, non-interference studies should be planned.
Neonate/ infant vaccine: Biomarker studies should be designed prior to the onset of Phase 2b clinical efficacy studies taking into consideration the limited volume of blood sample that can be drawn from infants. If the candidate vaccine is likely to be administered concomitantly with other vaccines recommended at birth (eg hepatitis B vaccine) or at later infant immunisation visits (e.g. EPI infants vaccines), non-interference studies should be planned.
Immunogenicity data from Phase 2b should be evaluated and be consistent with that observed in earlier studies and support continued development of the candidate vaccine. Biomarker samples collected during the Phase 2b study should be analysed for potential correlates of protection and/ or risk. These data, if available in time, should inform the development of the Phase 3 programme. A plan should be made for collection of further biospecimens for evaluation or discovery of biomarkers in Phase 3. Non-interference studies with concomitantly administered vaccines, if needed, should have been conducted during Phase 2b and no clinical or immunological interference demonstrated.
During the Phase 3 trial bio specimens have been collected. The investigational plan to identify a CoP should be developed based on the analysis of Phase 3 immunogenicity and efficacy data.
Biomarkers assays are performed on samples collected during the Phase 3 study. Biomarkers are measured and analysed to detect potential correlates of risk and/ or protection.