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| Status |
Public on Jun 16, 2023 |
| Title |
CD4 T Follicular Helper 1 Cells Promote HIV-1 Env Antibody Persistence |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Therefore, gaining insights into Tfh subsets promoting antibody persistence and functional capacity is crucial for vaccine design. We investigated the potential of inducing a mixed Tfh1/17 response to enhance HIV-1 Envelope (Env) antibodies to a DNA-prime/protein boost platform, utilizing rhesus macaques as our experimental model. Following immunization with Clade C gp140 protein formulated with cationic liposome-based formulation (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells, in contrast to the predominance of GC Tfh1 cells induced with gp140 formulated in monophosphoryl lipid A+QS-21 (MPLA). Analysis of lymph nodes, employing proteomic and transcriptional approaches, demonstrated robust induction of GC responses across vaccine platforms with distinct qualitative and quantitative effects elicited by MPLA versus CAF01. While the induction of GC Tfh1 cells with MPLA and GC Tfh1/17 cells with CAF01 resulted in comparable peak HIV-Env antibody levels, there was a notable difference in antibody persistence. The MPLA group demonstrated significantly greater antibody persistence at week 8 and up to 30 weeks after final immunization compared to CAF01. Inducing GC Tfh1 cells with MPLA furthermore enhanced tier 1 neutralization titers, antibody functions, and Env-specific IgG in the rectal mucosa. Notably, IFNγ+ Env-specific Tfh responses, both in blood and lymph nodes, were higher with MPLA and correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction may confer protective immunity against HIV.
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| Overall design |
Comparison of transcriptome profiles across CD4 subsets in two vaccine regimens
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| Contributor(s) |
Iyer SS, Verma A |
| Citation(s) |
37503150 |
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| Submission date |
Jun 13, 2023 |
| Last update date |
Dec 27, 2023 |
| Contact name |
Dhivyaa Rajasundaram |
| E-mail(s) |
dhr11@pitt.edu
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| Organization name |
University of Pittsburgh
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| Department |
Pediatrics
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| Street address |
4401 Penn Avenue
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15224 |
| Country |
USA |
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| Platforms (1) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
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| Samples (34)
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| Relations |
| BioProject |
PRJNA983281 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE234813_gene_count.txt.gz |
4.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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