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Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies.
- Source :
-
Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2020 Jan; Vol. 19 (1), pp. 155-166. Date of Electronic Publication: 2017 Oct 31. - Publication Year :
- 2020
-
Abstract
- Plasmodium falciparum malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. In a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. Despite multiple datasets for the Plasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development. This study characterizes 12 proteins from across the P. falciparum sexual-stages as possible TBV targets. Recombinant proteins are heterologously expressed as full-length ectodomains in a mammalian HEK293 cell system. The proteins recapitulate native parasite epitopes as assessed by indirect fluorescence assay and a proportion exhibits immunoreactivity when tested against sera from individuals living in malaria-endemic Burkina Faso and Mali. Purified IgG generated to the mosquito-stage parasite antigen enolase demonstrates moderate inhibition of parasite development in the mosquito midgut by the ex vivo standard membrane feeding assay. The findings support the use of rational screens and comparative functional assessments in identifying proteins of the P. falciparum transmission pathway and establishing a robust pre-clinical TBV pipeline.<br /> (© 2020 Nikolaeva et al.)
- Subjects :
- Adult
Animals
Anopheles parasitology
Epitopes immunology
Female
HEK293 Cells
Humans
Immunoglobulin G immunology
Malaria Vaccines immunology
Malaria, Falciparum epidemiology
Malaria, Falciparum virology
Male
Mali epidemiology
Mice
Mice, Inbred BALB C
Mosquito Vectors parasitology
Phosphopyruvate Hydratase immunology
Proteome
Proteomics methods
Vaccination
Antibodies, Blocking immunology
Malaria, Falciparum immunology
Malaria, Falciparum transmission
Plasmodium falciparum immunology
Protozoan Proteins immunology
Recombinant Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-9484
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular & cellular proteomics : MCP
- Publication Type :
- Academic Journal
- Accession number :
- 29089373
- Full Text :
- https://doi.org/10.1074/mcp.RA117.000036