P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions

The ookinete surface proteins (P25 and P28) are proven antimalarial transmission‐blocking vaccine targets, yet their biological functions are unknown. By using single (Sko) and double gene knock‐out (Dko) Plasmodium berghei parasites, we show that P25 and P28 share multiple functions during ookinete...

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Bibliographic Details
Published in:	The EMBO journal Vol. 20; no. 15; pp. 3975 - 3983
Main Authors:	Tomas, Ana M., Margos, Gabriele, Dimopoulos, George, van Lin, Leo H.M., de Koning-Ward, Tania F., Sinha, Ria, Lupetti, Pietro, Beetsma, Annette L., Rodriguez, Maria C., Karras, Marianna, Hager, Ariadne, Mendoza, Jacqui, Butcher, Geoffrey A., Kafatos, Fotis, Janse, Chris J., Waters, Andrew P., Sinden, Robert E.
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-08-2001 Blackwell Publishing Ltd Oxford University Press
Subjects:	Animals Anopheles - parasitology Antigens, Protozoan - genetics Antigens, Protozoan - physiology Antigens, Surface - genetics Antigens, Surface - physiology AP25 protein AP28 protein Aquatic insects Culicidae Digestive System - parasitology Epithelium knock-out Malaria Mosquitoes ookinete ookinetes P25 P25 protein P28 P28 protein Parasites Plasmodium Plasmodium berghei Plasmodium berghei - genetics Plasmodium berghei - growth & development Protozoan Proteins Vaccines Vector-borne diseases
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Summary:	The ookinete surface proteins (P25 and P28) are proven antimalarial transmission‐blocking vaccine targets, yet their biological functions are unknown. By using single (Sko) and double gene knock‐out (Dko) Plasmodium berghei parasites, we show that P25 and P28 share multiple functions during ookinete/oocyst development. In the midgut of mosquitoes, the formation of ookinetes lacking both proteins (Dko parasites) is significantly inhibited due to decreased protection against lethal factors, including protease attack. In addition, Dko ookinetes have a much reduced capacity to traverse the midgut epithelium and to transform into the oocyst stage. P25 and P28 are partially redundant in these functions, since the efficiency of ookinete/oocyst development is only mildly compromised in parasites lacking either P25 or P28 (Sko parasites) compared with that of Dko parasites. The fact that Sko parasites are efficiently transmitted by the mosquito is a compelling reason for including both target antigens in transmission‐blocking vaccines.
Bibliography:	istex:11ED56A4C43186F96E7B548DE26E138A9FBD8143 ArticleID:EMBJ7593895 ark:/67375/WNG-WQ1SCVS2-W ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.1093/emboj/20.15.3975