BioRxiv Preprint.pdf (2.74 MB)
0/0

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

Download (2.74 MB)
preprint
posted on 22.02.2019 by Miguel Julio Rodo, Elisa Nemes, One B. Dintwe, Mark Hatherill, Francesca Little, Thomas Scriba, Virginie Rozot
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.

History

Department/Unit

Statistics Pathology South African Tuberculosis Vaccine Initiative (SATVI)

Licence

Exports

Logo branding

Categories

Licence

Exports