T Cell Immunology l B Cell Immunology l Viral Biology l Structural Biology l Innate Immunity l Host Genetics l Vaccine Design l Adjuvant Development l Mucosal Immunity l NHP Correlates of Immunity of Live Attenuated SIV

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The T Cell Immunology Discovery Team is led by Dr. Andrew McMichael of Oxford University.  Investigators in T cell immunology will perform a comprehensive analysis of the ontogeny of anti-HIV-1 cellular responses in patients with acute HIV infection (AHI) compared to chronically infected patients.  In AHI studies, they will work to define “good” and “bad” anti-HIV-1 T cells using stimulating peptide sets that are both autologous and heterologous to the patient.  This team will also study samples from exposed and uninfected (EU) patients compared to unexposed and uninfected (UU) patient samples.  In EU studies, they will work to determine if, in a subset of EU samples, anti-HIV-1 immune responses are correlates of protection from HIV-1 infection.

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The B Cell Immunology Discovery Team is led by Dr. Barton Haynes of Duke University.  Investigators in B cell immunology will work to define the ontogeny of epitope-specific anti-HIV-1 binding and neutralizing antibodies as well as antigen specific B cells during acute HIV infection (AHI) in order to determine why broadly neutralizing antibodies are rarely made in AHI.

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The Viral Biology Discovery Team is led by Dr. Beatrice Hahn of the University of Alabama-Birmingham. Investigators in viral biology will sequence and characterize the transmitted virus in patients with acute HIV infection.  They will work to generate panels of transmitted viruses and to create and maintain the CHAVI transmitted HIV-1 sequence database for vaccine design and viral biology studies.  

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The Structural Biology Discovery Team is led by Dr. Joseph Sodroski of the Dana-Farber Cancer Institute and with Dr. Steven Harrison of the Children’s Hospital Boston.  Investigators in structural biology will focus on the structural properties of the HIV-1 trimer in order to develop a comprehensive picture of the conformational changes the virus undergoes during Acute HIV infection (AHI).  This research will assist investigators in the design of stable envelope forms of HIV-1 that can potentially induce broadly reactive neutralizing antibodies.   

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The Innate Immunity Discovery Team is led by Dr. Andrew McMichael of Oxford University and Dr. Persephone Borrow of the Edward Jenner Institute.  Investigators in innate immunity will study the functional properties of peripheral blood natural killer (NK) and dendritic cells (DC) in order to find a way to decrease the setpoint viral load and increase or maintain the levels of central memory CD4+ T cells.  By focusing on the NK and DC cells during the acute stages of HIV infection, investigators can ascertain their T cell stimulatory capacity and their ability to suppress HIV replication.  This research aims to develop vaccines that can recruit an accelerated innate immune response to HIV-1.

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The Host Genetics Discovery Team is led by Dr. David Goldstein of Duke University.  Investigators in host genetics will study samples from existing cohorts of Acute HIV Infection (AHI) and Exposed and Uninfected (EU) patients for genes that regulate host ability to control HIV-1 infection.  They will also analyze prospective cohorts in the CHAVI using candidate gene and genome-wide screens to define genes that contribute to control or prevention of HIV-1.  Coupled with the screens of candidate genes will be the capacity to study the biology of gene associations. 

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The Vaccine Design Discovery Team is led by Dr. Barton Haynes of Duke University.  Investigators in vaccine design will work in the Vector Development Core to design vectors, inserts and composite immunogens for testing in the Non-Human Primate Core.  Viable immunogens resulting from these immunogenicity studies will be considered for vaccine development. 

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The Adjuvant Development Discovery Team is led by Dr. Norm Letvin of Beth Israel Deaconess Medical Center.  Investigators in adjuvant development will work to develop novel adjuvants that optimize the immunogenicity of candidate HIV-1 vaccines produced by the CHAVI.

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The Mucosal Immunity Discovery Team is led by Dr. Robin Shattock of St. George’s Hospital in London.  Investigators in mucosal immunity will work to define the immune responses and host defenses at mucosal surfaces during HIV-1 transmission in order to develop vaccines that prevent mucosal transmission of HIV.

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The Discovery Team in Non-Human Primate Correlates of Immunity of Live Attenuated SIV (LAS) will be led by Dr. Norm Letvin of Beth Israel Deaconess Medical Center in collaboration with Louis Picker and Julie McElrath who are supported by funds from the Gates Foundation.  They will work to define the correlates of immune protection to live attenuated SIV and to superinfection.