Title
Identification of Plasmodium falciparum proteoforms from liver stage models
Date Issued
07 January 2020
Access level
open access
Resource Type
journal article
Author(s)
Winer B.
Edgel K.A.
Zou X.
Sellau J.
Hadiwidjojo S.
Garver L.S.
McDonough C.E.
Kelleher N.L.
Thomas P.M.
Villasante E.
Ploss A.
Naval Medical Research Command
Publisher(s)
BioMed Central Ltd.
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.
Volume
19
Issue
1
Language
English
OCDE Knowledge area
Enfermedades infecciosas
Medicina tropical
Subjects
Scopus EID
2-s2.0-85077683535
PubMed ID
Source
Malaria Journal
Sponsor(s)
This work was funded by the Bill and Melinda Gates Grand Challenges Explorations Round Nine Phase II awarded to VRG (OP1119033), the Military Infectious Diseases Research Program (VRG), the US Navy In-house Laboratory Independent Research Program (ILIR) supported by the Office for Naval Research (VRG), and the National Resource for Translational Proteomics NIH P41 GM108569 to NLK. A.P. is supported by a Burroughs Wellcome Fund Award (1015389) for Investigators in Pathogenesis and funds from Princeton University. B.Y.W. was supported by a training grant from the National Institutes of Healths (T32GM007388), is a recipient of an F31 NIH/National Research Service Award Ruth L. Kirschstein Predoctoral award from the National Institute of Allergy and Infectious Diseases and a graduate fellowship from the New Jersey Commission on Cancer Research.
Sources of information:
Directorio de Producción Científica
Scopus