Dataset Information

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses.

ABSTRACT: Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.

SUBMITTER: Hou N

PROVIDER: S-EPMC7174639 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low-Complexity Repetitive Epitopes of <i>Plasmodium falciparum</i> Are Decoys for Humoural Immune Responses.

Hou Nan N Jiang Ning N Ma Yu Y Zou Yang Y Piao Xianyu X Liu Shuai S Chen Qijun Q

Frontiers in immunology 20200415

Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the <i>Plasmodium falciparum</i> erythrocyte invasion-associated antigens with a purpose of understanding ...[more]

PMID: 32351503

Similar Datasets

Project description:Immunization with radiation-attenuated sporozoites (RAS) has been shown to protect against malaria infection, primarily through CD8 T cell responses, but protection is limited based on parasite strain. Therefore, while CD8 T cells are an ideal effector population target for liver stage malaria vaccine development strategies, such strategies must incorporate conserved epitopes that cover a large range of class I human leukocyte antigen (HLA) supertypes to elicit cross-strain immunity across the target population. This approach requires identifying and characterizing a wide range of CD8 T cell epitopes for incorporation into a vaccine such that coverage across a large range of class I HLA alleles is attained. Accordingly, we devised an experimental framework to identify CD8 T cell epitopes from novel and minimally characterized antigens found at the pre-erythrocytic stage of parasite development. Through in silico analysis we selected conserved P. falciparum proteins, using P. vivax orthologues to establish stringent conservation parameters, predicted to have a high number of T cell epitopes across a set of six class I HLA alleles representative of major supertypes. Using the decision framework, five proteins were selected based on the density and number of predicted epitopes. Selected epitopes were synthesized as peptides and evaluated for binding to the class I HLA alleles in vitro to verify in silico binding predictions, and subsequently for stimulation of human T cells using the Modular IMmune In-vitro Construct (MIMIC®) technology to verify immunogenicity. By combining the in silico tools with the ex vivo high throughput MIMIC platform, we identified 15 novel CD8 T cell epitopes capable of stimulating an immune response in alleles across the class I HLA panel. We recommend these epitopes should be evaluated in appropriate in vivo humanized immune system models to determine their protective efficacy for potential inclusion in future vaccines.

Dataset Information

Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses.

Publications

Low-Complexity Repetitive Epitopes of <i>Plasmodium falciparum</i> Are Decoys for Humoural Immune Responses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets