Discussion
TB, tuberculosis, and reduced wastage
TUBERCULOSIS
To our knowledge, this study represents the first thermostable subunit tuberculosis vaccine candidate to be evaluated in clinical testingThe specific objectives of the current Phase 1 trial were to evaluate the safety and immunogenicity of a thermostable single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the previously developed non-thermostable two-vial presentation. The safety profiles demonstrated here for both vaccine presentations were consistent with the generally mild reactogenicity evident in previous clinical trials of the two-vial vaccine presentationA Th1-type T cell response is considered favorable for protection against While B cell and antibody responses are not sufficient for protective efficacy against TB, their multiple complementary roles to T cell-mediated immunity are increasingly appreciated, and more clinical investigation is warranted in this regardThe multiple immunological assays, sample types, and time points employed in this study represent the most comprehensive clinical immunogenicity evaluation of the ID93 + GLA-SE vaccine candidate in healthy adults to date. Nevertheless, the study had several limitations, including the lack of placebo treatment groups, but these were deemed unnecessary due to previous clinical evaluation of ID93 + GLA-SE compared to ID93 alone or saline placeboThe impact of the thermostable single-vial formulation of ID93 + GLA-SE on vaccine manufacturing scalability and cost is another important consideration. We estimate that the excipient cost in the thermostable presentation would be approximately $0.15 more per dose than the non-thermostable composition at commercial scale. Furthermore, additional costs would be associated with the multi-day lyophilization processing time. However, these increased costs could be mitigated by the anticipated cost savings and reduced wastage associated with the less stringent storage requirements of the thermostable formulation compared to the non-thermostable presentation. Furthermore, lyophilization is already a well-established pharmaceutical processing technique that is employed in the production of many licensed vaccines.In summary, this Phase 1 clinical evaluation indicated that the thermostable single-vial presentation of ID93 + GLA-SE elicits a similar safety profile and a comparable or improved immunogenicity profile to the non-thermostable two-vial vaccine presentation. An effective thermostable TB vaccine would have major implications for global health impact. Furthermore, this study demonstrates proof-of-concept that an adjuvant-containing vaccine can be formulated in a single-vial thermostable presentation without detrimentally impacting clinical immunogenicity or safety characteristics.