Cores

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Clinical Sites Core

The CHAVI Clinical Sites Core is led by Dr. Myron Cohen of the University of North Carolina at Chapel Hill and is administered by Family Health International. This core oversees all observational clinical trials at sites performing one or more of CHAVI’s protocols. This core is responsible for developing clinical protocols, recruiting investigators, and developing a sample repository. The Clinical Sites Core is critical for generating the clinical samples for CHAVI work and for studying the biology of HIV-1 transmission.

Computational Biology and Mathematical Modeling Core

The Computational Biology and Mathematical Modeling Core is led by Dr. Bette Korber and Dr. Alan Perelson at Los Alamos National Laboratory.  Investigators in this core provide data analyses, evolutionary modeling, and analysis tools to CHAVI Discovery Teams.  Dr. Korber’s team analyzes viruses produced by the Viral Sequencing Core in order to characterize signatures of the transmitted virus.  Dr. Korber’s analyses also focus on understanding viral evolution from the moment of transmission to plasma viral load peak and viral biology during the very first days after transmission.  Dr. Perelson provides mathematical modeling of viral evolution during the earliest phase of HIV infection prior to an immune response.

Host Genetics Core

The Host Genetics Core is led by Dr. David Goldstein at Duke University. This Core runs whole genome association studies aimed at identifying human polymorphisms responsible for differences in host immune response to HIV. The Host Genetics Core is also studying the host genetic factors that influence inter-individual variability in the production of non-neutralizing anti-HIV antibodies. In addition, they perform functional studies on the genetic variants showing the highest association with HIV set point.

Immune Monitoring Core

The Immune Monitoring Core brings together the Duke Immune Monitoring group of Dr. Kent Weinhold, Dr. Guido Ferrari, Dr. David Montefiori, and Dr. Georgia Tomaras of the Binding Antibody Core.  The Immune Monitoring Core supports all CHAVI clinical trials work by providing comprehensive, state-of-the-art immunologic monitoring of HIV-specific B cell and T cell responses in support of CHAVI protocols.  In addition, the Immune Monitoring Core will work closely with Robin Shattock and the Mucosal Immunology Discovery Team to develop mucosal assays that are standardized and validated.

Monoclonal Antibody Core

The Monoclonal Antibody Core is led by Dr. Barton Haynes at Duke University and Dr. James Robinson at Tulane University.  This core is responsible for producing and purifying human and mouse monoclonal antibodies (Mabs) for HIV-1 neutralization and structural studies.  The Duke team, which includes Dr. Kwan-Ki Hwang, is working to generate antibodies derived from terminal ileum (INT), bone marrow (BMA), and peripheral blood (PBL) specimens from AHI patients as part of the Antibodyome Project.  The Tulane team constructs secondary hybridomas from selected EBV transformed cells to improve antibody production and maintains a repository of purified human and mouse MAbs, EBV transformed B cell lines, and hybridomas for CHAVI investigators.

Non-Human Primate Core

The Non-human Primate (NHP) Core is led by Dr. Norman Letvin of Beth Israel Deaconess Medical Center. This Core is studying non-human primates to determine the correlates of protection associated with superinfection, the nature of transmitted virus, the role of natural killer (NK) cells during primary simian immunodeficiency virus (SIV) infection, and the contribution of B cell responses in controlling SIV infection. This core also works with the Host Genetics Core in determining the mechanism responsible for vaccine-associated control of SIV/SHIV replication and identifying novel candidate genes whose expression may impact susceptibility to SIV infection.

Proteomics Core

The Proteomics Core is led by Dr. Munir Alam of Duke University. The Duke team supports the B cell Immunology Discovery Team by developing sensitive assays for the detection and characterization of B cell responses and by performing proteomics analyses on the apoptotic status of immune cells during HIV infection.  The Oxford team supports the Innate Immunity Discovery Team in characterizing molecules elevated in plasma in early acute HIV infection that are potentially involved in control of viral replication.

Structural Biology Core

The Structural Biology Core is co-led by Drs. Stephen Harrison at Harvard University and Joseph Sodroski from the Dana-Farber Cancer Institute. Investigators in this core study the structure of HIV-1 envelope glycoproteins in order to understand the conformational transitions that occur during transmission and infection and their biological impact.  Studies are focused on understanding how neutralizing antibodies, particularly those with breadth, interact with the HIV-1 envelope glycoproteins. This core is responsible for the production of HIV-1 gp140 trimers and their variants, further characterization of HIV-1 gp140 trimers, and the production of monoclonal antibodies to facilitate crystallization of gp140 trimer.

Vector Development Core

The Vector Development Core is led by Drs. Barton Haynes and Larry Liao at Duke University and by Norman Letvin of Beth Israel Deaconess Medical Center. Investigators in vector development carry out studies to express and characterize recombinant envelope proteins of transmitted/early HIV-1 viruses. This core is responsible for developing novel live recombinant vectors and novel polymer adjuvants and defining their effect on plasmid DNA expression and immunogenicity. Finally, this core is studying vaccine antigen clearance, including the relationship between duration of vaccine antigen expression and the generation of memory T cells, and the mechanism of vaccine antigen clearance and how it affects immunogenicity.

Viral Sequencing Core

The Viral Sequencing Core is led by Dr. Beatrice Hahn at the University of Alabama-Birmingham and includes Dr. Carolyn Williamson from the University of Cape Town, Dr. Ronald Swanstrom from the University of North Carolina at Chapel Hill, and Dr. Feng Gao from Duke University.  Investigators in this core derive HIV-1 envelope (env) and full-length genome sequences from acutely infected and chronically infected individuals using single genome amplification (SGA).  This core is also responsible for generating functional env clones from acute and chronic HIV-1 infections for biological studies.  The viral sequences are then used for transmission signature studies and for studies on the identification of the transmitted/founder virus.