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Mol Cell Proteomics. 2018 Jan;17(1):43-60. doi: 10.1074/mcp.RA117.000076. Epub 2017 Nov 21.

Quantitative Proteomic Profiling Reveals Novel Plasmodium falciparum Surface Antigens and Possible Vaccine Candidates.

Author information

1
From the ‡Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115.
2
§The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142.
3
¶Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow G12 8TA, UK.
4
‖Sanofi Biopharmaceutics Development, Framingham, Massachusetts 02142.
5
**Sanofi Pasteur Biologics, Cambridge, Massachusetts 02139.
6
‡‡Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
7
From the ‡Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115; matthias.marti@glasgow.ac.uk.

Abstract

Despite recent efforts toward control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes. These approaches have been successfully applied to the human-infective sporozoite stage. Both systemic and tissue-specific pathology during infection with the human malaria parasite P. falciparum is caused by asexual blood stages. Tissue tropism and vascular sequestration are the result of specific binding interactions between antigens on the parasite-infected red blood cell (pRBC) surface and endothelial receptors. The major surface antigen and parasite ligand binding to endothelial receptors, PfEMP1 is encoded by about 60 variants per genome and shows high sequence diversity across strains. Apart from PfEMP1 and three additional variant surface antigen families RIFIN, STEVOR, and SURFIN, systematic analysis of the infected red blood cell surface is lacking. Here we present the most comprehensive proteomic investigation of the parasitized red blood cell surface so far. Apart from the known variant surface antigens, we identified a set of putative single copy surface antigens with low sequence diversity, several of which are validated in a series of complementary experiments. Further functional and immunological investigation is underway to test these novel P. falciparum blood stage proteins as possible vaccine candidates.

PMID:
29162636
PMCID:
PMC5750850
DOI:
10.1074/mcp.RA117.000076
[Indexed for MEDLINE]
Free PMC Article

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