SOCIAL & SCIENTIFIC SYSTEMS, INC.

"Several projects were funded under this award. Project #1 - To evaluate and qualify new assays for infant diagnosis and viral load monitoring of HIV under standard laboratory conditions prior to field testing. Outputs: 1 or 2 manuscripts Deliverables to date: Specimens have been requested and diagnostic kits have been ordered. We are in the process of obtaining permission to hire a new technician to perform the work. Once we find a suitable person the specimens and kits should be here ready for testing. Project #2 - To purchase a Ultra High Performance Liquid Chromatography (UHPLC) instrument to support this clinical trial through the IMPAACT consortium. A requirement of drug manufacturers and preferred by federal regulators is that the assay be developed using mass spectrometry technology, as it is the most sensitive and specific technology available. In addition, sample collection volume is restricted in young infants and children so a highly sensitive method is needed which requires only very small sample volumes. Therefore, this UHPLC will serve as the front end for a new dedicated mass spectrometer (API 5000). The parent project proposes to measure S/GSK1349572 concentrations in plasma samples collected from pediatric study participants using a reverse-phase UHPLC assay, coupled to a triple quadrupole mass spectrometer (MS-MS) for detection. This method will be developed in the UAB IMPAACT Pharmacology Specialized Laboratory (PSL), under the direction of Dr. Acosta, to support this pivotal pediatric licensure clinical trial. Project #3: P1088: ?A Phase II Study to Assess the Safety and Immunogenicity of an Inactivated Swine-Origin H1N1 Influenza Vaccine in HIV-1 Perinatally Infected Children and Youth? in which the primary objectives include evaluation of vaccine immunogenicity as defined by HAI titer and secondary objectives include other characteristics of antibody response and cell mediated immunity. This project shall apply a systems biology approach to understand the nature of the immune response to the H1N1 vaccine in the patients in P1088. University of Miami in collaboration with IMPAACT Investigators shall identify relevant biological pathway profiles characterized by gene expression signatures and shall correlate the profiles with the HAI Antibody titers following the influenza A H1N1 vaccine in HIV-infected children and adolescents in P1088. The data shall used to develop a classifier, which could potentially be applied to predict the outcome of future vaccinations. The group expects to be able to assess both the innate and adaptive immune responses following the second vaccination. The group shall perform microarray analysis using RNA extracted from the 2.5 mL whole blood collected in PAXgene tubes from the first 3 scheduled time points. Arrays shall be run on the Illumina platform on the Vaccine and Genetics Therapy Institute-FL Genomics Core facility. The group shall preprocess, normalize, and filter for genes that show variance across the samples, and format a gene/sample expression matrix to be used as input for linear modeling using the BioConductor package ?Linear models for microarray analysis? (LIMMA) (11). Gene Set Enrichment Analysis (GSEA) shall then be performed to identify relevant biological pathways that are associated with the biological outcomes. Finally, the gene signature pathways shall be identified using a manual process with the incorporation of the lists of differentially expressed genes and the results from the GSEA, and that signature shall form the basis for developing a classifier for screening whole blood for responses to H1N1 vaccination in HIV infected children."

Clarification of Codes