Mitchell LeFebvre

Enhancing Whole Parasite Plasmodium Vaccination Strategies

The Plasmodium species are the causative agent of malaria, a devastating mosquito born disease that is responsible for millions of infections and hundreds of thousands of deaths each year. Current therapies to treat malaria suffer from emerging parasite drug resistance, and there are no readily deployable vaccines despite decades of research. Sporozoites, the infectious form of the parasite, can be attenuated with radiation (RAS) and injected intravenously (IV) to induce protective immunity in mice and humans. Unfortunately, this vaccination strategy is not field practical in its current state, as it involves multiple large IV doses. Other vaccination strategies using subcutaneous, intramuscular, and intradermal delivery of subunit vaccines are more readily administrable in the field, but induce short lived, non-sterilizing immune responses.

We can use fundamental understanding of the immunological requirements for protection from Plasmodium in mouse models to guide human vaccination efforts. My work combines whole parasite vaccination (RAS) and different subunit vaccine approaches in inbred mouse strains to develop protective vaccine strategies more optimized for clinical efficacy, as measured by lower dose requirements and more efficient delivery methods. I also study the mechanisms of protective vaccine-induced responses, with particular attention to memory CD8 T cell populations.



Lefebvre MN, Drewry LL, Pewe LL, Hancox LS, Reyes-Sandoval A, Harty JT. Cutting Edge: Subunit Booster Vaccination Confers Sterilizing Immunity against Liver-Stage Malaria in Mice Initially Primed with a Weight-Normalized Dose of Radiation-Attenuated Sporozoites. J Immunol. 2021 Dec 1;207(11):2631-2635. doi: 10.4049/jimmunol.2100818. Epub 2021 Oct 29. PMID: 34716185; PMCID: PMC8612975.

Medical School: University of Iowa (MSTP)
Mitchell Lefebvre
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3-501 BSB
United States

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