Christine Boutros
UC San Francisco
“Proteome-wide Humoral Immune Profiling in Central Nervous System Valley
Fever using Programmable Phage Display”
Valley Fever is a fungal disease caused by Coccidioides that can disseminate to the central nervous system, leading to severe and often fatal meningitis. To improve diagnosis and treatment, we developed an antibody profiling library using bacteriophage to identify VF meningitis-specific antibodies produced in early disease. This approach identified 46 highly immunogenic protein segments, which can serve as early diagnostic markers and potential therapeutic targets.
ABSTRACT
Valley Fever (VF) is a fungal disease endemic to the southwestern United States, caused by the pathogen Coccidioides. Case rates have risen 675% since 1998, partly due to climate change expanding the endemic region. Though primarily a pulmonary disease, VF is a significant public health concern because it can infect immune- competent individuals and, in some cases, spread to the central nervous system, causing severe and often fatal inflammation, called meningitis. Like most fungal neuroinfections, VF meningitis lacks well-defined treatment standards. Current diagnostics have variable sensitivity and specificity, leading to false positives in patients with other fungal infections.
The humoral immune response, primarily mediated by antibodies, plays a key role in protecting against external pathogens. To improve detection and treatment, we developed a novel antibody profiling library using bacteriophage. These phages express Coccidioides proteins and we identify VF meningitis-specific antibodies produced in early disease. We identified 46 out of ~200,000 highly immunogenic protein segments that present early that are unique to VF and preliminarily associated with virulence.
These strong diagnostic and therapeutic candidates may enhance early detection and targeted treatments.
SUBMIT COMMENT OR QUESTION