Nikolaeva D., Illingworth J. J., Miura K., Alanine D. G. W., Brian I. J., Li Y. Y., Fyfe A. J., Da D. F., Cohuet Anna, Long C. A., Draper S. J., Biswas S. (2020). Functional characterization and comparison of Plasmodium falciparum proteins as targets of transmission-blocking antibodies. Molecular and Cellular Proteomics, 19 (1), p. 155-166. ISSN 1535-9476.
Titre du document
Functional characterization and comparison of Plasmodium falciparum proteins as targets of transmission-blocking antibodies
Année de publication
2020
Auteurs
Nikolaeva D., Illingworth J. J., Miura K., Alanine D. G. W., Brian I. J., Li Y. Y., Fyfe A. J., Da D. F., Cohuet Anna, Long C. A., Draper S. J., Biswas S.
Source
Molecular and Cellular Proteomics, 2020,
19 (1), p. 155-166 ISSN 1535-9476
The malaria agent Plasmodium falciparum continues to evade control efforts. 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. We demonstrate 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. 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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010078034]
Identifiant IRD
fdi:010078034
