We are now accepting applications for the Penn CFAR Developmental Pilot Awards! Applications are due December 17th, 2018. The complete RFA can be found here.
Dr. Drew Weissman, who has developed nucleoside-modified mRNA-lipid nanoparticle (LNP) as a novel platform for vaccines, showed that the vaccine and LNPs specifically induce high levels of T follicular helper cells (Tfh). Tfh cells form germinal centers (GC) and drive GC B cells to proliferate, somatically mutate, class switch, and form long-term memory, which are critical for HIV vaccine development. In addition to HIV, the vaccine platform has applications to many different viral, bacterial, and parasitic pathogens.
- Link to article: Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.
Dr. Mohamed Abdel-Mohsen and a multidisciplinary team from Wistar, Penn and several other institutions, found that CD32, previously implicated as a marker of the HIV latent reservoir, is actually expressed preferentially on a subset of activated CD4+ T cells enriched for transcriptionally active HIV. This has important implications for identifying and targeting HIV latency in infected people. More information here.
- Link to article: CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.
Dr. Laura Su and an international, transdisciplinary team have authored an article in Science Immunology that focuses on how follicular helper T cells (Tfh) play an essential role in shaping B-cell mediated antibody responses. The Su lab employed mass cytometry and TCR sequencing to directly examine the Tfh response to HIV and reported oligoclonal expansion of a functionally-restricted subset of Tfh cells in HIV infected lymph nodes. This lack of polyfunctionality may contribute to Tfh cell pathology in HIV infection and correlated with impaired isotype switching of B cells in the lymph nodes.
- Link to article: The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes.
A study led by Marcus Buggert in Mike Betts’ lab demonstrated that a unique type of CD8+ T cells residing in HIV-infected lymphoid tissue may play a critical role in long term control of HIV replication. More than 99% of viral replication occurs in lymphoid tissues, which is the key site for controlling virus. These T resident memory cells (Trm) have distinct attributes from other T cells, and may central in control of HIV. This study was enabled by key collaborations through the Reservoirs and Tissue Immunology Scientific Working Group relied on support provided by the Penn CFAR Clinical Core.
- Link to article: Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.
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