Jennifer S. Armistead, PhD, MPH (PhD Student, MMI)
My research interests are focused on malaria transmission biology, particularly as it pertains to the discovery and investigation of new transmission-blocking interventions. Malaria is a parasitic infection that is transmitted from human to human through the bite of an infectious Anopheles mosquito. In an era in which malaria elimination, and even eradication, is the goal, vaccines that interrupt the transmission of malaria will be essential. These transmission-blocking vaccines (TBVs) seek to induce antibodies in immunized humans that when taken up in an infectious blood meal, will inhibit Plasmodium parasite maturation in the mosquito midgut. TBVs may target sexual or mosquito stages of the parasite or antigens on the mosquito midgut that are required for parasite invasion of this tissue. By arresting parasite development within the mosquito vector, TBVs prevent the subsequent cascade of human infections.
With a background in vector biology, I am particularly interested in understanding which macromolecules on the mosquito midgut play key roles in the hierarchical invasion process of Plasmodium ookinetes and how these vector-parasite interactions might be harnessed to develop mosquito-based interventions for the interruption of malaria transmission. How these processes differ among P. falciparum and P. vivax, the two main contributors to malaria morbidity and mortality, is even more fascinating and has important implications for TBV design and implementation. As a trained field entomologist, confirming the relevance of laboratory findings in malaria endemic settings has been a focus of my research.
As a PhD student in the Dinglasan laboratory, I have been involved in the investigation and development of a mosquito-based malaria TBV that targets a mosquito midgut aminopeptidase (AnAPN1), which has been shown to be essential for the development of P. falciparum and the murine malaria parasite, P. berghei, in laboratory assays. I have been involved in all aspects of the pre-clinical evaluation of AnAPN1 as a TBV antigen to determine its potency, histopathology, and functionality in murine and non-human primate models. However, the primary objective of my thesis research has been to uncover the immunological and biochemical mechanisms underlying the transmission-blocking functionality of anti-AnAPN1 antibodies. Immunological aspects of this work focused on identifying Plasmodium transmission-blocking epitopes and assessing their conservation among different Anopheles-Plasmodium systems, but also included antibody-antigen kinetics and isotyping studies. In addition, my efforts to characterize the enzymatic activity of AnAPN1, its ability to bind Plasmodium ookinetes, and how anti-AnAPN1 antibodies affect these functions have improved our understanding of how this vaccine interferes with malaria transmission.