Author:
Winer Benjamin,Edgel Kimberly A.,Zou Xiaoyan,Sellau Julie,Hadiwidjojo Sri,Garver Lindsey S.,McDonough Christin E.,Kelleher Neil L.,Thomas Paul M.,Villasante Eileen,Ploss Alexander,Gerbasi Vincent R.
Abstract
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.
Funder
Bill and Melinda Gates Foundation
Burroughs Wellcome Fund
National Institute of General Medical Sciences
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Parasitology
Cited by
2 articles.
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