Dataset Information

Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults.

ABSTRACT:

Background

Mass cytometry, or CyTOF (Cytometry by Time-of-Flight), permits the simultaneous detection of over 40 phenotypic and functional immune markers in individual cells without the issues of spectral overlap seen in traditional flow cytometry.

Methods

In this study, we applied CyTOF to comprehensively characterize the circulating immune cell populations in elderly individuals both before and after administration of an investigational adjuvanted protein vaccine against respiratory syncytial virus (RSV) in a Phase 1a trial. Antigen-specific T cell responses to RSV by IFN? ELISPOT had been observed in most but not all recipients in the highest dose cohort in this trial. Here, CyTOF was used to characterize the cellular response profile of ELISPOT responders and non-responders in this vaccine dose cohort.

Results

Both CD4⁺ and CD8⁺ T cell antigen-specific IFN? responses were observed. Principal components analysis revealed baseline differences between responders and non-responders, including differences in activated (HLA-DR⁺) CD4⁺ and CD8⁺ T cells, which were higher in non-responders versus responders. Using viSNE to analyze RSV-responsive CD4⁺ and CD8⁺ T cells, we also found increased expression of HLA-DR, CCR7, CD127 and CD69 in non-responders versus responders.

Conclusions

High parameter CyTOF can help profile immune components associated with differential vaccine responsiveness.

SUBMITTER: Lingblom CMD

PROVIDER: S-EPMC5987461 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults.

Lingblom Christine M D CMD Kowli Sangeeta S Swaminathan Nithya N Maecker Holden T HT Lambert Stacie L SL

Journal of translational medicine 20180605 1

<h4>Background</h4>Mass cytometry, or CyTOF (Cytometry by Time-of-Flight), permits the simultaneous detection of over 40 phenotypic and functional immune markers in individual cells without the issues of spectral overlap seen in traditional flow cytometry.<h4>Methods</h4>In this study, we applied CyTOF to comprehensively characterize the circulating immune cell populations in elderly individuals both before and after administration of an investigational adjuvanted protein vaccine against respira ...[more]

PMID: 29866115

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Project description:This phase II study evaluated the effect of chloroquine on the specific CD8(+) T-cell responses to and the safety of a booster dose of investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01(B) vaccine containing 10 μg of recombinant fusion protein (F4) adjuvanted with the AS01(B) adjuvant system. Healthy adults aged 21 to 41 years, primed 3 years before with two F4/AS01(B) doses containing 10 or 30 μg of F4 (ClinicalTrials.gov registration number NCT00434512), were randomized (1:1) to receive the F4/AS01(B) booster administered alone or 2 days after chloroquine (300 mg). F4-specific CD8(+)/CD4(+) T-cell responses were characterized by intracellular cytokine staining and lymphoproliferation assays and anti-F4 antibodies by enzyme-linked immunosorbent assays (ELISAs). No effect of chloroquine on CD4(+)/CD8(+) T-cell and antibody responses and no vaccine effect on CD8(+) T-cell responses (cytokine secretion or proliferation) were detected following F4/AS01(B) booster administration. In vitro, chloroquine had a direct inhibitory effect on AS01(B) adjuvant properties; AS01-induced cytokine production decreased upon coincubation of cells with chloroquine. In the pooled group of participants primed with F4/AS01(B) containing 10 μg of F4, CD4(+) T-cell and antibody responses induced by primary vaccination persisted for at least 3 years. The F4/AS01(B) booster induced strong F4-specific CD4(+) T-cell responses, which persisted for at least 6 months with similar frequencies and polyfunctional phenotypes as following primary vaccination, and high anti-F4 antibody concentrations, reaching higher levels than those following primary vaccination. The F4/AS01(B) booster had a clinically acceptable safety and reactogenicity profile. An F4/AS01(B) booster dose, administered alone or after chloroquine, induced robust antibody and F4-specific CD4(+) T-cell responses but no significant CD8(+) T-cell responses (cytokine secretion or proliferation) in healthy adults. (This study has been registered at ClinicalTrials.gov under registration number NCT00972725).

Dataset Information

Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults.

Background

Methods

Results

Conclusions

Publications

Baseline immune profile by CyTOF can predict response to an investigational adjuvanted vaccine in elderly adults.

Similar Datasets

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