Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230.

Autor: MacDonald NJ; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Nguyen V; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Shimp R; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Reiter K; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Herrera R; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Burkhardt M; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Muratova O; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Kumar K; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Aebig J; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Rausch K; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Lambert L; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Dawson N; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Sattabongkot J; the Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand, and., Ambroggio X; the Rosetta Design Group LLC, Burlington, Vermont 05401., Duffy PE; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Wu Y; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852., Narum DL; From the Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland 20852, dnarum@niaid.nih.gov.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2016 Sep 16; Vol. 291 (38), pp. 19913-22. Date of Electronic Publication: 2016 Jul 18.
DOI: 10.1074/jbc.M116.732305
Abstrakt: 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.
(© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze: MEDLINE