David Koelle
University of Washington, WA·Microbiology & Immunology
Herpes-family viruses stay in the body for life and flare up repeatedly, and the immune system's local response in skin and mucosal tissue is what keeps them in check. Both projects ask how the immune cells that gather at the site of infection recognize these viruses, and how that knowledge can be turned into treatments.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
- Topics
varicella zoster virus
shingles
herpes zoster
- Grants
- 2 known grants, through Jul 2028
What they work on
- Expand the collection of varicella zoster virus-specific human monoclonal antibodies cloned from shingles skin biopsies and map their fine specificity against viral envelope, tegument, enzyme, and nuclear proteins.
- Test these antibodies for antiviral function in assays of cell-to-cell viral spread and neutralization, to assess whether they could serve as a defined alternative to pooled varicella zoster immune globulin.
- Characterize tertiary lymphoid structures, tissue clusters of T and B cells, in shingles biopsies using advanced microscopy and spatial technologies, and measure T cell-B cell cooperation in vitro.
- Optimize a 'string of pearls' poly-epitope CD8 T cell immunotherapeutic for HSV-2 so it covers diverse viral strains and HLA-diverse human populations while avoiding immunodominance, self cross-reactivity, and cytotoxicity.
- Rank nucleic acid delivery formats, including mucosal homing strategies, by testing prototype immunotherapeutics in mice in an immune memory context, with a mutated gD2 glycoprotein included to boost CD4 T cells.
- Test efficacy of the optimized candidate in the guinea pig genital herpes therapy model as advanced preclinical development.
More about the research
One project reads out the antibodies made by B cells inside shingles rashes; the other designs an immune therapy to boost virus-specific T cells in genital herpes. Together they treat the infected tissue itself as the place to look for protective immunity.
Why it matters
Varicella zoster virus causes shingles pain, eye infections with vision loss, encephalitis, and severe fetal and newborn infections, and current antivirals and vaccines leave unmet needs. Antibodies cloned from shingles skin could become a molecularly defined replacement for the pooled antiserum now given to patients, which may be valuable for pregnant women without prior immunity. Genital herpes affects roughly 15% of U.S. adults and is incurable; a T cell-boosting immunotherapeutic could reduce recurrences, symptoms, viral shedding, and transmission.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Stefan Oliver
Stanford University, CA·Biophysics
Determine the near-atomic structure of the varicella-zoster virus gB/gH-gL complex, the machinery that fuses viral and cell membranes, using single-particle cryo-electron microscopy on complexes kept in their native lipid environment.
Justin Bailey
Johns Hopkins University, MD·Microbiology & Immunology
Test whether a dengue vaccine's serotype composition determines the balance, neutralizing potency, and durability of serotype-specific versus cross-reactive memory B cells and monoclonal antibodies, and whether those responses predict protection after controlled human challenge with serotype 2.
James B Mclachlan
Tulane University of Louisiana, LA·Microbiology & Immunology
Determine how intradermal immunization with the detoxified enterotoxin adjuvant dmLT combined with bacterial outer membrane vesicles directs vaccine-specific T cells to mucosal tissues, tracked with MHC class I and II tetramers.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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