Strong Vaccine-Elicited Th1-Biased CD4 T cell Response Abrogates SIV Vaccine Efficacy
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE93835 | GEO | 2018/03/01
REPOSITORIES: GEO
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Project description:The primary objective of this study was to evaluate response to a SIV DNA-based vaccine that was adminstered via vivo electroporation (EP) in rhesus macaques to further understand the molecular correlates of protection against SIV. In this study, rhesus macaques were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES), followed by EP. At eight month post-vaccination, animals were challenged with SIV. Standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis were performed to determine the host response to each vaccine regimen. The overall study was designed to evaluate the response to a SIV-DNA vaccination administered to animals via intramuscular electroporation. Chinese rhesus macaques were divided into three treatment groups (n=6 animals per group): Control (no vaccination), DNA vaccine alone (pCSIVgag, pCSIVpol, pCSIVenv), DNA vaccine with RANTES adjuvant (pCSIVgag, pCSIVpol, pCSIVenv, pmacRANTES). Eight months following the last vaccination, animals were infected with 25 MID of SIVmac251 and response to infection was monitored. RNA for microarray analysis was isolated from fresh PBMCs that were isolated from individual animals and treated overnight with a pool of overlapping SIV pol peptides or mock treated. Samples for microarray analysis were taken longitudinally at 8 months post-vaccination (pre-SIV challenge; biological n=5-6 per group for each treatment; technical n=2 for each sample) and at day 10 post-SIV challenge (n=5-6 per group for each treatment; technical n=2 for each sample).
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