A comparison of antigen-specific T cell responses induced by six novel tuberculosis vaccine candidates (BioRxiv preprint)

Pre-print submitted to BioRxiv.Abstract: Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large - scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen - specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette - Guérin (BCG). We propose that the antigen - specific immune response induced by such vaccines provides an objective, data - driven basis for prioritisation of vaccine candidates for efficacy testing. We analyze d frequencies of antigen - specific CD4 and CD8 T cells expressing IFN γ, IL - 2, TNF and/or IL - 17 from adolescents or adults, with or without Mycobacterium tuberculosis ( M.tb ) infection, who received MVA85A, A ERAS - 402, H1:IC31, H56:IC31, M72/AS01 E, ID93 + GLA - SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co - expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen - specific CD4 T cell responses expressing Th1 cytokines; levels of IL - 17 - expressing cells were low or not detected. In M.tb - uninfected and - infected individuals, M72/AS01 E induced higher memory Th1 cytokine - expressing CD4 T cell response s than other novel vaccine candidates. Cytokine co - expression profile s of memory CD4 T cells induced by different novel vaccine candidates were alike. Our study suggests that the T cell response feature which most differentiated between the TB vaccine candidates was response magnitude, whilst functional profiles suggested a lack of response diversity. Since M72/AS01 E induced the highest memory CD4 T cell response it demonstrated the best vaccine take. In the absence of immunological correlates of protection the likelihood of finding a protective vaccine by empirical testing of candidates may be increased by the addition of candidates that induce distinct immune characteristics.