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  • The EMBO Journal (2001) 20, 3975 - 3983
  • doi:10.1093/emboj/20.15.3975

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

Ana M. Tomas1, Gabriele Margos2, George Dimopoulos3, Leo H.M. van Lin1, Tania F. de Koning-Ward1, Ria Sinha2, Pietro Lupetti4, Annette L. Beetsma2, Maria C. Rodriguez2, Marianna Karras2, Ariadne Hager2, Jacqui Mendoza2, Geoffrey A. Butcher2, Fotis Kafatos3, Chris J. Janse1, Andrew P. Waters1 and Robert E. Sinden1

  1. Leiden University Medical Centre, Laboratory of Parasitology, PO Box 9605, 2300 RC Leiden, The Netherlands
  2. Imperial College of Science, Technology and Medicine, Biology Department, Sir Alexander Fleming Building, Imperial College Road, London SW7 2AZ, UK
  3. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
  4. Unit of Electron Microscopy and Cryotechniques, Dipartimento Biologia Evolutiva, Università di Siena, Via P.A. Mattioli 4, 53100 Siena, Italy

Correspondence to:

Robert E. Sinden, E-mail: r.sinden@ic.ac.uk

Received 14 May 2001; Accepted 4 June 2001

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.

  • Keywords:

    • knock-out,
    • ookinete,
    • P25,
    • P28,
    • Plasmodium