Biography

The Earnest lab studies the diversity and effectiveness of antibody responses to viral infection. Our primary focus is on mosquito-borne viruses that are spread in tropical regions. These include the flaviviruses dengue (DENV) and Zika (ZIKV) as well as alphaviruses chikungunya (CHIKV) and Mayaro (MAYV) viruses. For all of these viruses, antibody FC-mediated effector functions play an important role in disease severity. For the alphaviruses, these effector functions are generally protective but for flaviviruses the story is more complex. DENV- and ZIKV- mediated illness can be made worse by cross-reactive but non-neutralizing antibodies through a mechanism called antibody-dependent enhancement (ADE). ADE is mediated by antibody effector functions and can lead to severe disease outcomes including death. Due to the importance and duality of antibody effector functions, we want to measure how the diversity of antibodies changes in individuals and populations over time and how this affects protection from infection or exacerbation of disease.

We strive to bridge the gap between field observation and laboratory investigation. To do this, we lead and participate in clinical field trials to better understand viral transmission in areas of endemic transmission. We have particular interest in following antibody selection and memory B cell formation in people experiencing natural infection in endemic areas. Samples collected in these areas allow us to perform in-depth serological testing as well as cutting-edge single cell sequencing to identify and follow virus-specific B cells over time. We hope to define protective or harmful “antibody trajectories” over time and multiple exposures in individuals and populations. The findings from these studies will help us design better therapies and vaccines as well as inform disease control methods on the ground in endemic areas.