Transcriptomics

Dataset Information

3

VIA of EM CD8 T cells in vaccinated monkeys


ABSTRACT: The goal of an effective AIDS vaccine is to generate immunity that will prevent HIV-1 acquisition. Despite limited progress towards this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies elicited by DNA prime/rAd5 boost vaccination with SIVmac239 Gag/Pol and Env provided protection against pathogenic SIVsmE660 acquisition after repeated mucosal challenge. Here, we report that SIV-specific CD8+ T cells elicited by that vaccine lowered both peak and set-point viral loads in macaques that became infected despite vaccination. These SIV-specific CD8+ T cells showed strong virus inhibitory activity (VIA) and displayed an effector memory (EM) phenotype. VIA correlated with high levels of CD107a mobilization and perforin expression in SIV-specific CD8+ T cells. Remarkably, both the frequency and the number of Gag CM9-specific public clonotypes were strongly correlated with VIA mediated by EM CD8+ T cells. The ability to elicit such virus-specific EM CD8+ T cells might contribute substantially to an efficacious HIV/AIDS vaccine, even after breakthrough infection. Gag CM9-specific EM CD8+ T cells (CD28 low CD95 high tetramer+) from SIV-negative macaques at 12 wks post-DNA/rAd5 immunization were sorted by flow cytometry for microarray studies. RNA samples from strong VIA animals with (n=3) or without (n=6) CM9 peptide stimulation, along with CM9 peptide stimulated samples from weak VIA animals (n=2) were prepared using the Illumina beads station assay and hybridized to the Illumina HumanHT-12 version 4 Expression BeadChip.

ORGANISM(S): Macaca mulatta  

SUBMITTER: Adrian B McDermott   David A Price  Daniel C Douek  Francois Lefebvre  Ling Shen  Jorge R Almeida  Constantinos Petrovasa  Norman L Letvin  Richard A Koup  Martha Nason  Mario Roederer  Takuya Yamamoto  Elias K Haddad  Srinivas S Rao  Wendy W Yeh  David I Wolinsky  Gary J Nabel  Matthew J Johnson 

PROVIDER: E-GEOD-35628 | ArrayExpress | 2012-06-14

SECONDARY ACCESSION(S): GSE35628PRJNA152473

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Virus inhibition activity of effector memory CD8(+) T cells determines simian immunodeficiency virus load in vaccinated monkeys after vaccine breakthrough infection.

Yamamoto Takuya T   Johnson Matthew J MJ   Price David A DA   Wolinsky David I DI   Almeida Jorge R JR   Petrovas Constantinos C   Nason Martha M   Yeh Wendy W WW   Shen Ling L   Roederer Mario M   Rao Srinivas S SS   McDermott Adrian B AB   Lefebvre Francois F   Nabel Gary J GJ   Haddad Elias K EK   Letvin Norman L NL   Douek Daniel C DC   Koup Richard A RA  

Journal of virology 20120314 10


The goal of an effective AIDS vaccine is to generate immunity that will prevent human immunodeficiency virus 1 (HIV-1) acquisition. Despite limited progress toward this goal, renewed optimism has followed the recent success of the RV144 vaccine trial in Thailand. However, the lack of complete protection in this trial suggests that breakthroughs, where infection occurs despite adequate vaccination, will be a reality for many vaccine candidates. We previously reported that neutralizing antibodies  ...[more]

Similar Datasets

2012-01-01 | S-EPMC3347297 | BioStudies
2013-01-01 | S-EPMC3545953 | BioStudies
1000-01-01 | S-EPMC3911762 | BioStudies
2013-01-01 | S-EPMC3622154 | BioStudies
2014-01-01 | S-EPMC4054456 | BioStudies
1000-01-01 | S-EPMC4130272 | BioStudies
| GSE75567 | GEO
2008-01-01 | S-EPMC2493343 | BioStudies
2013-08-01 | E-GEOD-42459 | ArrayExpress
1000-01-01 | S-EPMC6183272 | BioStudies