Identification of Plasmodium falciparum proteoforms from liver stage models
Posted on 2020-01-08 - 04:57
Abstract Background 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. Methods 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. Results These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold. Conclusions 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.
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Winer, Benjamin; Edgel, Kimberly; Zou, Xiaoyan; Sellau, Julie; Hadiwidjojo, Sri; Garver, Lindsey; et al. (2020). Identification of Plasmodium falciparum proteoforms from liver stage models. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4808859.v1
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AUTHORS (12)
BW
Benjamin Winer
KE
Kimberly Edgel
XZ
Xiaoyan Zou
JS
Julie Sellau
SH
Sri Hadiwidjojo
LG
Lindsey Garver
CM
Christin McDonough
NK
Neil Kelleher
PT
Paul Thomas
EV
Eileen Villasante
AP
Alexander Ploss
VG
Vincent Gerbasi