Title | Identification of Plasmodium falciparum proteoforms from liver stage models. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Winer, B, Edgel, KA, Zou, X, Sellau, J, Hadiwidjojo, S, Garver, LS, McDonough, CE, Kelleher, NL, Thomas, PM, Villasante, E, Ploss, A, Gerbasi, VR |
Journal | Malar J |
Volume | 19 |
Issue | 1 |
Pagination | 10 |
Date Published | 2020 Jan 07 |
ISSN | 1475-2875 |
Keywords | Animals, Antigens, Protozoan, Disease Models, Animal, Epitopes, T-Lymphocyte, Female, Hepatocytes, Immunity, Cellular, Liver, Malaria Vaccines, Malaria, Falciparum, Mass Spectrometry, Mice, Plasmodium falciparum, Proteomics, Serum Albumin, Human |
Abstract | <p><b>BACKGROUND: </b>Immunization with attenuated malaria sporozoites protects humans from experimental malaria challenge by mosquito bite. Protection in humans is strongly correlated with the production of T cells targeting a heterogeneous population of pre-erythrocyte antigen proteoforms, including liver stage antigens. Currently, few T cell epitopes derived from Plasmodium falciparum, the major aetiologic agent of malaria in humans are known.</p><p><b>METHODS: </b>In this study both in vitro and in vivo malaria liver stage models were used to sequence host and pathogen proteoforms. Proteoforms from these diverse models were subjected to mild acid elution (of soluble forms), multi-dimensional fractionation, tandem mass spectrometry, and top-down bioinformatics analysis to identify proteoforms in their intact state.</p><p><b>RESULTS: </b>These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold.</p><p><b>CONCLUSIONS: </b>This work provides proof-of-concept for the validity of this mass spectrometry/bioinformatic approach for future studies seeking to reveal malaria liver stage antigens towards vaccine development.</p> |
DOI | 10.1186/s12936-019-3093-3 |
Alternate Journal | Malar J |
PubMed ID | 31910830 |
PubMed Central ID | PMC6947969 |
Grant List | GM108569 / GM / NIGMS NIH HHS / United States P41 GM108569 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States |