Journal article
Functional characterization and comparison of Plasmodium falciparum proteins as targets of transmission-blocking antibodies
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 1.8MB, Terms of use)
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(Preview, Not applicable (or unknown), pdf, 69.0KB, Terms of use)
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- Publisher copy:
- 10.1074/mcp.ra117.000036
Authors
+ Jenner Investigator
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- Funding agency for:
- Draper, S
- Biswas, S
- Grant:
- 106917/Z/15/Z
+ Lister Institute Research Prize Fellow
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- Funding agency for:
- Draper, S
- Grant:
- 106917/Z/15/Z
+ Wellcome Trust
More from this funder
- Funding agency for:
- Illingworth, J
- Draper, S
- Grant:
- TranslationalMedicinePhDProgramme[grantnumber092873/z/10/z
- Infection,Immunology
- 106917/Z/15/Z
+ National Institutes of Health
More from this funder
- Funding agency for:
- Nikolaeva, D
- Grant:
- OxCam Program
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Journal:
- Molecular and Cellular Proteomics More from this journal
- Volume:
- 19
- Issue:
- 1
- Pages:
- 155-166
- Publication date:
- 2017-10-31
- Acceptance date:
- 2017-10-31
- DOI:
- EISSN:
-
1535-9484
- ISSN:
-
1535-9476
- Pmid:
-
29089373
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:742342
- UUID:
-
uuid:2b08d42b-2751-4244-bae5-edc4a3e7b8f8
- Local pid:
-
pubs:742342
- Source identifiers:
-
742342
- Deposit date:
-
2017-11-03
- ARK identifier:
Terms of use
- Copyright holder:
- Nikolaeva et al.
- Copyright date:
- 2017
- Rights statement:
- Copyright © 2020 Nikolaeva et al. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license.
- Licence:
- CC Attribution (CC BY)
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