The Genomics and Bioinformatics Core (G/BC), based at the Vaccine &Gene Therapy Institute in Florida, shall apply innovative bioinformatics and systems biology methods to the assessment of the transcriptional changes and immune correlates associated with stimulation by specific antigens following the gene-modified vs. wildytpe RhCMV/SIV vector immunization, RhCMV/SIV immunizations with a heterologous prime, and vaccine efficacy regimens. Our specific objective is to define the gene expression signatures of Wildtype RhCMV/SIV vector-elicited SIV-specific T cell responses and compare and contrast the gene signatures with those elicited by heterologously primed wt RhCMV/SIV vectors and with replication-deficient, tropism- modified, and immune evasion-modifed RhCMV/SIV vectors. We will also strive to determine whether the gene expression signatures vary from animal to animal given the same vector to predict protection and identify correlates of immune protection. The G/BC will work closely with the projects and other cores to provide consultation and data for use in cross-platform validation and vector/regimen decisions in the efficacy experiments.
Aims of the Core 1. Provide a centralized sample, reporting, and data management and distribution framework. 2. Perform the microarray assay from RNA extraction through platform hybridization. 3. Provide biostatistical processing and analysis of microarrays and quantitative RT-PCR (QPCR) validation. 4. Provide first (Y1-Y3) and final (Y4-Y5) integrated immune correlate analysis for vector/regimen selection and model building.
The Genomics and Bioinformatics Core will help the Program achieve its objective of a safe and efficacious HIV/AIDS vaccine design based on CMV vectors by advising the Projects, integrating the data streams, and ultimately by providing the functional genomics data and immune models ofthe molecular and gene expression signatures that will correlate with the immunogenicity and efficacy profiles of the various RhCMV/SIV vectors and regimens.
|Früh, Klaus; Picker, Louis (2017) CD8+ T cell programming by cytomegalovirus vectors: applications in prophylactic and therapeutic vaccination. Curr Opin Immunol 47:52-56|
|McMichael, Andrew J; Picker, Louis J (2017) Unusual antigen presentation offers new insight into HIV vaccine design. Curr Opin Immunol 46:75-81|
|Hansen, Scott G; Wu, Helen L; Burwitz, Benjamin J et al. (2016) Broadly targeted CD8? T cell responses restricted by major histocompatibility complex E. Science 351:714-20|
|Hansen, Scott G; Sacha, Jonah B; Hughes, Colette M et al. (2013) Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 340:1237874|
|Hansen, Scott G; Piatak Jr, Michael; Ventura, Abigail B et al. (2013) Immune clearance of highly pathogenic SIV infection. Nature 502:100-4|
|Masopust, David; Picker, Louis J (2012) Hidden memories: frontline memory T cells and early pathogen interception. J Immunol 188:5811-7|
|Malouli, Daniel; Nakayasu, Ernesto S; Viswanathan, Kasinath et al. (2012) Reevaluation of the coding potential and proteomic analysis of the BAC-derived rhesus cytomegalovirus strain 68-1. J Virol 86:8959-73|