Microbiology

Katherine Doll

Katherine Doll

Address: 3-501 BSB
Phone: (319) 335-9919
Email: katherine-doll@uiowa.edu

Mentor: John T. Harty, PhD

Undergraduate Institution: University of Minnesota

Research Description

Despite decades of research, malaria remains a global health crisis. Malaria is caused by infection by Plasmodium parasites, which exhibit a complex multi-host, multi-stage lifecycle. Infection starts when a mosquito injects the sporozoite form of the parasite during bloodmeal feeding. The sporozoites first establish asymptomatic infection in the liver (liver-stage) before differentiating into the merozoites, the form of the parasite that infects red blood cells (blood stage) and causes symptoms of malaria. Recently, the anti-liver-stage RTS,S anti-malarial subunit vaccine has entered into the final stages of Phase III clinical trials. However, despite the demonstrated reduction in disease severity in vaccinated individuals, immunity is non-sterilizing (blood-stage infection still occurs, albeit at reduced levels). Conversely, vaccination using attenuated whole Plasmodium sporozoites has achieved sterilizing immunity in human and rodent models (no detectable blood stage infection).

I am working to identify and characterize the cellular basis for potent, sterilizing anti-Plasmodial immunity in rodent models following vaccination with different formulations of attenuated Plasmodium sporozoites. Current methods involve examining quantitative and qualitative aspects of Plasmodium-specific CD8 and CD4 T cell responses, as well as measuring anti-Plasmodial humoral responses. Thus far my work has demonstrated a critical role for Plasmodium-specific, vaccine-induced CD8 T cells. Further, I have shown that exposure to liver-stage and blood-stage parasite antigens is required to achieve potent sterilizing immunity. I hypothesize that exposure of the vaccinated host to both liver- and blood-stage parasite antigens provides additional protective antigenic targets for T cells and humoral responses; this requirement is not met by subunit vaccination or vaccination approaches that only expose the host to liver-stage antigens.


Publication(s)

Liang X, Hall JW, Yang J, Yan M, Doll K, Bey R, Ji Y. Identification of single nucleotide polymorphisms associated with hyperproduction of alpha-toxin in Stapylococcus aureus. (2011) PLoS One.

Doll KL, Butler NS, Harty JT. Tracking the total CD8 T cell response following whole Plasmodium vaccination. (2011) Methods in Molecular Biology: Malaria. Submitted.