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Series GSE256418 Query DataSets for GSE256418
Status Public on Feb 26, 2024
Title Cell-mediated Immune Response Signature to AAV Capsid in Cynomolgus Monkeys
Organism Macaca fascicularis
Experiment type Expression profiling by high throughput sequencing
Summary Cell-mediated immune (CMI) responses to adeno-associated virus (AAV) can lead to both tissue damage and loss of therapeutic transgene expression. Identifying robust biomarkers of CMI and understanding CMI mechanisms can be help to helpful in clinical practice and in advancement of AAV gene therapies. The present work evaluated PBMCs from non-human primates (NHP) before and 14 days following immunization with AAV9 capsid. PBMCs were stimulated in vitro with AA9 capsid peptides to evaluate CMI responses by IFN- ELISPOT, intracellular cytokines and activation markers by flow cytometry, secreted cytokines by ELISAMSD, and transcriptional responses by RNAseq. AAV peptide stimulation produced a robust IFN- ELISPOT response at 14 days. Flow cytometry revealed an increase in IFN- positive CD4 and CD8 cells, IL2 positive CD4 cells, and TNF positive CD4 cells. An increase in the CXCR3 ligands IP-10 and I-TAC were detected both inas secreted proteins. The most robust changes in response to AAV stimulation and strongest correlations to ELISPOT response were revealed by RNAseq, including transcripts encoding IFN- and transcripts encoding , IP-10 and I-TAC , and many downstream transcripts and several IFN-independent pathways. These data provide evidence that a gene signature, or CXCR3 ligand transcripts or protein could serve as robust and sensitive alternatives to ELISPOT for detection of CMI, andCMI and warrant further benchmarking in human samples.
Overall design PBMCs were isolated from cynomolgus monkeys before or 14 days after treatment with AAV9. Cells were then stimulated in vitro overnight with either DMSO, a CD3 positive control, or AAV9 capsid peptides to evalute cell-mediated immune responses to the AAV.
Contributor(s) Virgen-Slane R, Lanz TA, Lee SG, Qian J
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Submission date Feb 22, 2024
Last update date Feb 26, 2024
Contact name Richard Virgen-Slane
Organization name Pfizer
Department Global Computational Safety Science, DSRD
Street address 0777 Science Center Drive, CB4-2131, Pfizer La Jolla
City San Diego
State/province CA
ZIP/Postal code 92121
Country USA
Platforms (1)
GPL22523 Illumina NextSeq 500 (Macaca fascicularis)
Samples (102)
GSM8098236 dmso+pid 1-X per treatment/timepoint group rep 1
GSM8098237 dmso+pid 1-X per treatment/timepoint group rep 2
GSM8098238 dmso+pid 1-X per treatment/timepoint group rep 3
BioProject PRJNA1079376

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Supplementary file Size Download File type/resource
GSE256418_raw_counts.txt.gz 1.6 Mb (ftp)(http) TXT
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