title: P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions.
abstract: 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.
authors.affiliation: Leiden University Medical Centre, Laboratory of Parasitology, PO Box 9605, 2300 RC Leiden, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Tomas
authors.forename: G
authors.initials: G
authors.lastname: Margos
authors.forename: G
authors.initials: G
authors.lastname: Dimopoulos
authors.forename: L H
authors.initials: LH
authors.lastname: van Lin
authors.forename: T F
authors.initials: TF
authors.lastname: de Koning-Ward
authors.forename: R
authors.initials: R
authors.lastname: Sinha
authors.forename: P
authors.initials: P
authors.lastname: Lupetti
authors.forename: A L
authors.initials: AL
authors.lastname: Beetsma
authors.forename: M C
authors.initials: MC
authors.lastname: Rodriguez
authors.forename: M
authors.initials: M
authors.lastname: Karras
authors.forename: A
authors.initials: A
authors.lastname: Hager
authors.forename: J
authors.initials: J
authors.lastname: Mendoza
authors.forename: G A
authors.initials: GA
authors.lastname: Butcher
authors.forename: F
authors.initials: F
authors.lastname: Kafatos
authors.forename: C J
authors.initials: CJ
authors.lastname: Janse
authors.forename: A P
authors.initials: AP
authors.lastname: Waters
authors.forename: R E
authors.initials: RE
authors.lastname: Sinden
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000953:Antigens, Protozoan / Q000235:genetics / Q000502:physiology*; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology*; D004064:Digestive System / Q000469:parasitology; D004848:Epithelium; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development*; D015800:Protozoan Proteins
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; C067548:ookinete antigen P25, Plasmodium