Application and utility of mass cytometry in vaccine development

Abstract

Mass cytometry enables highly multiplexed profiling of cellular immune responses in limited-volume samples, advancing prospects of a new era of systems immunology. The capabilities of mass cytometry offer expanded potential for deciphering immune responses to infectious diseases and to vaccines. Several studies have used mass cytometry to profile protective immune responses, both postinfection and postvaccination, although no vaccine-development program has yet systematically employed the technology from the outset to inform both candidate design and clinical evaluation. In this article, we review published mass cytometry studies relevant to vaccine development, briefly compare immune profiling by mass cytometry to other systems-level technologies, and discuss some general considerations for deploying mass cytometry in the context of vaccine development.-Reeves, P. M., Sluder, A. E., Raju Paul, S., Scholzen, A., Kashiwagi, S., Poznansky, M. C. Application and utility of mass cytometry in vaccine development.

Rational Design and In Vivo Characterization of Vaccine Adjuvants

“…Due to little overlap between the heavy metal isotopes, the number of antibodies used for each assay can be increased compared with flow cytometry. However, the data acquisition rate is low at 300 to 500 events/s compared with the acquisition rates of flow cytometry at orders of magnitude at 10 3 to 10 5 events/ s. 86,87 Thus, 36 different antibodies were used to identify subpopulations of human CD8 + memory and effector T cells. The functionality of subpopulations of CD8 + T cells were identified by principal component analysis and combinatorial diversity achieved by Boolean gating, which were distinct for different virus-specific CD8 + T cells.…”

“…88 These data analysis approaches are suitable for simultaneous assessment of different immune cell populations due the large amounts of data generated using CyTOF. 87 Thus, differences in cytokine and receptor expression patterns of immune cell subsets (CD4 + and CD8 + T cells, B cells and monocytes) were assessed for naïve and influenzavaccinated mice after influenza challenge. 87 CyTOF has potential for assessing changes in type and functionality of immune cell subsets after immunization with different subunit vaccine adjuvants.…”

“…87 Thus, differences in cytokine and receptor expression patterns of immune cell subsets (CD4 + and CD8 + T cells, B cells and monocytes) were assessed for naïve and influenzavaccinated mice after influenza challenge. 87 CyTOF has potential for assessing changes in type and functionality of immune cell subsets after immunization with different subunit vaccine adjuvants. It may be possible to identify correlates of protection in disease challenge models or show differences between different adjuvants.…”

“…Furthermore, the method requires low sample volumes enabling longitudinal studies using blood samples. 87 The cytokine levels in response to stimulation with antigen can also be assessed by using ELISPOT, where the released cytokines are captured by cytokine-specific antibodies adsorbed to the well. 89,90 This approach was used to quantify the expression of IFN-γ, IL-4, and IL-2 in mice immunized with virus-like particles, which showed that concomitant co-stimulation with poly(I:C) increased the cytokine responses.…”

Vaccines Meet Big Data: State-of-the-Art and Future Prospects. From the Classical 3Is (“Isolate–Inactivate–Inject”) Vaccinology 1.0 to Vaccinology 3.0, Vaccinomics, and Beyond: A Historical Overview

“…New cutting-edge technologies include next-generation sequencing (NGS) techniques [RNASeq ( 19 ) and large-scale B- and T-cell receptor sequencing ( 20 , 21 )], mass cytometry (CyTOF) ( 22 ), and peptide/protein arrays ( 23 ). Data produced by molecular biology and NGS as well as by bioinformatics ( 24 ) can be used to perform mechanistic reductionist studies but can be also exploited to comprehensively capture immune dynamics and interactions ( 25 ), carrying out, for instance, network analysis or systems biology (the so-called “systems vaccinology”).…”