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Aspects of immunity for the AMA-1 family of molecules in humans and non-human primates malarias

Abstract

The apical membrane antigen (AMA-1) family of malaria merozoite proteins is characterised by a high degree of inter-species conservation. Evidence that the protein (PK66/AMA-1) from the simian parasite Plasmodium knowlesi was protective in rhesus monkeys suggested that the 83kDa P. falciparum equivalent (PF83/AMA-1) should be investigated for protective effects in humans. Here we briefly review pertinent comparative data, and describe the use of an eukaryotic full length recombinant PF83/AMA-1 molecule to develop a sensitive ELISA for the determination of serological responses in endemic populations. The assay has revealed surprisingly high levels of humoral response to this quantitatively minor antigen. We also show that PK66/AMA-1 inhibitory mAb's are active against merozoites subsequent to release from schizont-infected red cells, further implicating AMA-1 molecules in red cell invasion.

Plasmodium falciparum; Plasmodium knowlesii; AMA-1; PK66; PF83; merozoite; seroepidemiology


ABSTRACT

Aspects of immunity for the AMA-1 family of molecules in humans and non-human primates malarias

A. W. Thomas1

D. Narum1

A. P. Waters2

J. F. Trape3

C. Rogier4

A. Gonçalves5

V. Rosario6

P. Druilhe7

G. H. Mitchell8

D. Dennis8

TNO, BPRC, Laboratory for Parasitology, Rijswijk, The Netherlands

University of Leiden, Department Parasitology, Leiden, The Netherlands

Laboratoire de Paludologie, Dakar, Senegal

Service d'Epidemiologie, Dakar, Senegal

UNL, CMDT, IHMT. Dept. S. Publica, Lisboa, Portugal

UNL, Centro de Malária e Outras Doenças Tropicais, Lisboa, Portugal

Institute Pasteur, Paris, France

Guy's Hospital, The Medical School, London, England

The apical membrane antigen (AMA-1) family of malaria merozoite proteins is characterised by a high degree of inter-species conservation. Evidence that the protein (PK66/AMA-1) from the simian parasite Plasmodium knowlesi was protective in rhesus monkeys suggested that the 83kDa P. falciparum equivalent (PF83/AMA-1) should be investigated for protective effects in humans. Here we briefly review pertinent comparative data, and describe the use of an eukaryotic full length recombinant PF83/AMA-1 molecule to develop a sensitive ELISA for the determination of serological responses in endemic populations. The assay has revealed surprisingly high levels of humoral response to this quantitatively minor antigen. We also show that PK66/AMA-1 inhibitory mAb's are active against merozoites subsequent to release from schizont-infected red cells, further implicating AMA-1 molecules in red cell invasion.

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Publication Dates

  • Publication in this collection
    15 June 2009
  • Date of issue
    1994
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