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Self Progress Report Abstracts continued

Submitted August 13, 2010

The Vaccine Immunology Statistical Center (VISC) collaborations with CAVD members expanded to include new projects with previous collaborators as well as several new groups. These collaborative projects included work on study designs, data collection, statistical analysis, and software development and produced new data models, data management and analytic systems, and several manuscripts.

The VISC’s workload is driven by the needs of CAVD investigators and labs as well as the needs of the HIV research community in general. Thus, we have seen more interest in antibodies and preclinical (mouse, NHP) studies in the past year.

Data systems development by the VISC continues apace, driven by the priorities of CAVD investigators and analysis needs identified by VISC statisticians. Recent work includes improvements to existing systems to handle neutralizing antibody, ELISA/Luminex, and ELISpot assays, as well as development of new systems for ICS flow, microarray, sequence data, and the specific data management needs associated with nonhuman primate and mouse studies. All of this work is conducted in collaboration with key contacts at CAVD member labs which include; BIDMC-Seaman lab, NVITAL-Bailer lab, IAVI-NY-McDermott, Duke-Montefiori and Tomaras labs, VRC-Roederer, MIL-Greenberg, and OHSU-Picker.

The VISC continues to assemble teams with expertise in biostatistics, immunologic assays, and information systems to assist CAVD investigators. We seek to have the flexibility and skills necessary to build ongoing collaborative relationships and to be able to address their emerging needs quickly. Establishing contacts with key investigators and lab personnel and developing working relationships is essential for the VISC’s continued success providing statistical collaboration and data management services to the CAVD.

Submitted January 19, 2010

The Vaccine Immunology Statistical Center is organized within the CAVD to provide services in the areas of statistical design and data analysis, a central repository for key CAVD studies, and support for laboratory data management.  Our diverse staff has expertise in the areas of biostatistics, immunologic assays, bioinformatics, data management, and information systems.   We ensure that CAVD studies are efficient by providing state-of-the-art statistical methods and, when required, develop novel methods. 

Areas of methodological development and consultation by the VISC include work on analytic methods for assessing immunological correlates of risk and of protection, the design of repeated low-dose challenge non-human primate studies, signal processing and normalization of flow cytometry-based assays, models for the analysis of multivariate outcomes in mouse immunogenicity experiments, and the analysis of high-dimensional immunologic checkerboard data.

The VISC continues to work closely with the CAVD Vaccine Immune Monitoring Consortia – the CA VIMC and the CTC VIMC – in the testing and standardization of antibody and T Cell assays within and between core labs.  These efforts include labs based in the United States, Europe, Africa and Asia.  Current assay projects include the standardized TZM-bl neutralizing antibody assay, the clinical ELISpot assay (Transfer Study and Internal Quality Assurance), the clinical ICS Flow assay (pre-Qualification and Qualification), and the CTC VIMC’s nonhuman primate core assays (ELISpot and ICS Flow).

We also design data models for novel immunologic assays and engineer integrated data pipelines from lab instruments to upload data into the CAVD central data repository.  Finally, we support service data access, data sharing, and collaboration through a customized web portal available to the large community of CAVD investigators.

 
Submitted August 1, 2009

The Vaccine Immunology Statistical Center is organized within the CAVD to provide services in the areas of statistical design and data analysis, a central repository for key CAVD studies, and support for laboratory data management. Our diverse staff has expertise in the areas of biostatistics, immunologic assays, bioinformatics, data management, and information systems. We ensure that CAVD studies are efficient by providing state-of-the-art statistical methods and, when required, develop novel methods. Specific areas of novel methodological development are the design of repeated low-dose challenge non-human primate studies, the analysis of immunologic checkerboard data, signal processing and normalization of flow cytometry-based assays, and network models for the analysis of multivariate outcomes in mouse immunogenicity experiments. We also design data models for novel immunologic assays and engineer integrated data pipelines from lab instruments to the CAVD central data repository. Finally, we support service data access, data sharing, and collaboration through a customized web portal available to the large community of CAVD investigators.

 
Submitted January 15, 2009 (Interim Report)

Through the last half of 2008, the Vaccine Immunology Statistical Center’s collaborations with CAVD members expanded to include new projects with previous collaborators as well as several new groups. These collaborative projects included work on study designs, data collection, statistical analysis, and software development and produced new data models, data management and analytic systems, and several manuscripts.

The VISC’s workload is driven by the needs of CAVD investigators and labs as well as the needs of the HIV research community in general. Thus we have seen more interest in antibodies and preclinical studies in the past year.

Recent VISC projects:

Analytics:

  • Tier I/II Virus Panel (Montefiori VIMC): Analysis of a panel of 106 pseudoviruses in the TZM-bl assay run against 6 pools of sera and several reagents and monoclonal antibodies. The VISC created novel data visualizations and statistical analyses. Data systems and software developed for this project will be utilized and expanded for new and larger antibody projects planned for 2009.
  • Analysis of Low-level Neutralization (Zolla-Pazner VDC): Development of robust methods to distinguish statistically significant, low-level neutralization using area under the titration curve summary measures. VISC statisticians created new statistical methods that have generated interest from many CAVD investigators beyond those involved in the initial collaboration.
  • Other recent analytic projects included: Mapping the specificities of neutralizing antibodies in broadly cross-reactive plasma (Morris-Gray NICD); Novel statistical analyses of mouse immonology data to infer specific mechanisms of vaccine action on primary endpoints (MIL-Greenberg/Blattman); and Statistical analyses of data from nonhuman primate experiments (Lehner VDC and IAVI-McDermott).

Study Designs:

  • Study designs for a Phase I clinical trial and an NHP experiment (Ho VDC)
  • Peptide reagent testing (Bailer-NVITAL/Koup VIMC)
  • ICS Flow assay qualification testing (Roederer-VRC/Koup VIMC)
  • PBMC Cryopreservation testing (von Briesen HSC/Koup VIMC)

Data systems development by the VISC continues apace, driven by the priorities of CAVD investigators and analysis needs identified by VISC statisticians. Recent work includes improvements to existing systems to handle neutralizing antibody, ELISA/Luminex, and ELISpot assays, as well as development of new systems for ICS flow, microarray, sequence data, and the specific data management needs associated with nonhuman primate and mouse studies. All of this work is conducted in collaboration with key contacts at CAVD member labs which include; BIDMC-Seaman lab, NVITAL-Bailer lab, IAVI-NY-McDermott, Duke-Montefiori and Tomaras labs, VRC-Roederer, MIL-Greenberg, and OHSU-Picker.

The VISC continues to assemble teams with expertise in biostatistics, immunologic assays, and information systems to assist CAVD investigators. We seek to have the flexibility and skills necessary to build ongoing collaborative relationships and to be able to address their emerging needs quickly. Establishing contacts with key investigators and lab personnel and developing working relationships is essential for the VISC’s continued success providing statistical and data management services to the CAVD.

 
Submitted August 1, 2008

Throughout the Vaccine Immunology Statistical Center’s second year, increasing numbers of CAVD collaborators made use of VISC resources to help with the management, analysis, interpretation and sharing of data. These multidisciplinary interactions have lead to an overall higher quality of science performed. Specifically, VISC statisticians, programmers and data managers have developed a deeper knowledge of emerging biological assays and investigators have developed deeper appreciation of the important statistical issues associated with vaccine studies, immunologic assays, and the resulting data.

The number of users of VISC’s Atlas web portal continues to grow as more features are added. Eleven CAVD studies utilizing the CAVD Central Service Facilities for performing standardized endpoint assays have been completed and the results – including the study designs, the assay summary tables, as well as the raw assay data - have been made available to all CAVD members on the Atlas portal. Atlas is being used to register new CAVD study designs, assist the CAVD assay labs with data management, exchange data and reports with VDC investigators, and help VISC scientific staff to communicate and share information both internally and externally. The VISC continues to assemble teams with expertise in biostatistics, immunologic assays, and information systems to assist CAVD investigators. We seek to have the flexibility and skills necessary to address their emerging needs quickly and to build ongoing collaborative relationships. As we move forward we intend to work more with collaborators on best practices for study designs, develop new and improved online tools, and settle upon standard nomenclatures and data formats to facilitate data sharing and communication.

 
Submitted January 16, 2008 (Interim Report)

The VISC has developed and deployed the essential elements of a system to enable data from studies performed by CAVD sites to populate a central CAVD Study Database. The CAVD Study Registration module is a web-based interactive tool used to facilitate determination of study design, specify the flow of specimens from study sites to VIMC endpoint laboratories, and structure the central study database to receive study data.

Assay data pipelines from VIMC laboratories to VISC have been built and installed for the core set of CAVD study endpoint assays. These data pipelines include integrated data quality control processes as well as a security model that enables appropriate control of access to data during its curation. In addition, an interactive web-based general purpose assay data tool has been built that enables the rapid definition of a data model and implementation of a data pipeline for research and development assays performed by the VIMC R&D laboratories. This tool facilitates the capture of data from novel, cutting-edge assays and the integration of this data into the central study database providing additional scientific value to VDCs.  A initial version of a database of standard materials, reagents and nomenclature for defining immunization regimens and laboratory assays has been developed in collaboration with the CAVD Alliance Management (AM) group. These “meta-data” or value lists will serve as the wiring that links the immunology assay data and study information as well as ensure that the CAVD collaborators are all ‘speaking the same language.’ The development of this dynamic data resource and process for its maintenance has involved principals of the CAVD Central Service Facilities as well as several of the VDCs.

In the past year, VISC statisticians have collaborated with several VDCs and VIMCs on study designs and data analyses. The design of non-human primate challenge experiments has been an important activity with collaboration with Thomas Lehner’s VDC as an initial example and subsequent work with Dan Barouch (from Norm Letvin’s VDC) and John Mascola (from the NIH Vaccine Research Center) on designs to assess the role of prior Ad5 immunity and potential enhancement of susceptibility to infection due to vaccination with an Ad5 vector vaccine. This latter activity is motivated by the unexpected results from HVTN 502 (STEP) trial of Merck’s Ad5-based HIV vaccine candidate. This work has led to further collaborations with Dan Barouch regarding the ranking and selection of multiple adenovirus-based regimens (alternatives to Ad5) in NHP challenge experiments. Preliminary discussions with Dan Barouch have also taken place regarding his interest in NHP studies to assess different concepts of vaccine insert design (motif-optimized transgene sequences, heterogenous insert prime/boost strategies). Statistical collaboration with David Montefiori on the design of his serotype discovery program have been initiated and have involved analyses of preliminary NAb checkerboard data sets augmented with pseudovirus env sequence data.  Finally, work on developing statistical study designs and analyses of data from assay proficiency studies has been conducted for the NAb TZM-bl assay (Montefiori) and ELISpot (Koup). 

A key to ongoing success of the VISC is developing contacts and coordinating efforts within the CAVD.  In 2007, we worked on proactive alliance building with respect to coalescing Central Service Facilities into integrated package for VDCs and expect these efforts to continue to grow and yield benefits through 2008 and beyond.

 
Submitted August 1, 2007

The overarching goal of the Vaccine Immunology Statistical Center (VISC) is to provide a mechanism for bringing together immunologic data from the myriad preclinical and clinical studies of HIV-related immunogens being conducted within the Collaboration for AIDS Vaccine Discovery (CAVD) with the requisite standardization and structure to enable analyses of the combined database, and thereby achieve important scientific insights that otherwise would be impossible to attain.

To achieve this goal, we are building an infrastructure for the management, analysis, and sharing of immunologic assay data, and providing access to this infrastructure via our web-based interface, Atlas.

We have focused our initial efforts towards

  • Completing data pipelines for standardized endpoint assays from VIMC labs: Neutralizing Antibody, ELISA, ELISpot, and ICS.
  • Building data pipelines for emerging research and development assays from VIMC R&D labs.
  • Collaborating with other CAVD Central Service Facilities (CSFs) to expand the user base among VDCs to register studies and utilize CSF resources.
  • Offering free “walk up” biostatistical consulting activities for assay and vaccine study designs, and biostatistical analysis services.
  • Providing software tools, technical support, and training to lab staff to promote the use of standard tools and best practices.

In the years ahead, we plan on deepening our collaboration with key CAVD labs and VDC sites to gain a more complete understanding of their needs. We will continue to enhance the Atlas website to facilitate data sharing and the application of the best analytic methods. Through these partnerships and innovative software tools, we expect to build a more comprehensive lab data/IT infrastructure to advance the goals of the CAVD, and the Vaccine Enterprise.

 
For general questions about the CAVD or the content of the these pages, please contact alliance.management@cavd.org.
For technical issues with the website, please contact portalsupport@cavd.org.