Publication: Structural and immunological characterization of recombinant 6-cysteine domains of the plasmodium falciparum sexual stage protein Pfs230
Issued Date
2016-09-16
Resource Type
ISSN
1083351X
00219258
00219258
Other identifier(s)
2-s2.0-84987816118
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Biological Chemistry. Vol.291, No.38 (2016), 19913-19922
Suggested Citation
Nicholas J. MacDonald, Vu Nguyen, Richard Shimp, Karine Reiter, Raul Herrera, Martin Burkhardt, Olga Muratova, Krishan Kumar, Joan Aebig, Kelly Rausch, Lynn Lambert, Nikiah Dawson, Jetsumon Sattabongkot, Xavier Ambroggio, Patrick E. Duffy, Yimin Wu, David L. Narum Structural and immunological characterization of recombinant 6-cysteine domains of the plasmodium falciparum sexual stage protein Pfs230. Journal of Biological Chemistry. Vol.291, No.38 (2016), 19913-19922. doi:10.1074/jbc.M116.732305 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42928
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Title
Structural and immunological characterization of recombinant 6-cysteine domains of the plasmodium falciparum sexual stage protein Pfs230
Abstract
Development of a Plasmodium falciparum (Pf) transmission blocking vaccine (TBV) has the potential to significantly impact malaria control. Antibodies elicited against sexual stage proteins in the human bloodstream are taken up with the blood meal of the mosquitoes and inactivate parasite development in the mosquito. In a phase 1 trial, a leading TBV identified as Pfs25-EPA/Alhydrogel® appeared safe and immunogenic, however, the level of Pfs25-specific antibodies were likely too low for an effective vaccine. Pfs230, a 230-kDa sexual stage protein expressed in gametocytes is an alternative vaccine candidate. A unique 6-cysteine-rich domain structure within Pfs230 have thwarted its recombinant expression and characterization for clinical evaluation for nearly a quarter of a century. Here, we report on the identification, biochemical, biophysical, and immunological characterization of recombinant Pfs230 domains. Rabbit antibodies generated against recombinant Pfs230 domains blocked mosquito transmission of a laboratory strain and two field isolates using an ex vivo assay. A planned clinical trial of the Pfs230 vaccine is a significant step toward the potential development of a transmission blocking vaccine to eliminate malaria.