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

Ana M. Tomas, Gabriele Margos, George Dimopoulos, Leo H.M. Van Lin, Tania F. De Koning-Ward, Ria Sinha, Pietro Lupetti, Annette L. Beetsma, Maria C. Rodriguez, Marianna Karras, Ariadne Hager, Jacqui Mendoza, Geoffrey A. Butcher, Fotis Kafatos, Chris J. Janse, Andrew P. Waters, Robert E. Sinden

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3975-3983
Number of pages9
JournalEMBO Journal
Volume20
Issue number15
DOIs
StatePublished - Aug 1 2001
Externally publishedYes

Keywords

  • Knock-out
  • Ookinete
  • P25
  • P28
  • Plasmodium

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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