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Invasion-inhibitory antibodies inhibit proteolytic processing of apical membrane antigen 1 of Plasmodium falciparum merozoites.
Dutta, Sheetij; Haynes, J David; Moch, J Kathleen; Barbosa, Arnoldo; Lanar, David E.
Afiliação
  • Dutta S; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. sheetij.dutta@na.amedd.army.mil
Proc Natl Acad Sci U S A ; 100(21): 12295-300, 2003 Oct 14.
Article em En | MEDLINE | ID: mdl-14526103
ABSTRACT
Apical membrane antigen 1 (AMA-1) is a promising vaccine candidate for Plasmodium falciparum malaria. Antibodies against AMA-1 of P. falciparum (PfAMA-1) interrupt merozoite invasion into RBCs. Initially localized within the apical complex, PfAMA-1 is proteolytically processed and redistributed circumferentially on merozoites at about the time of their release and invasion into RBCs. An 83-kDa precursor form of PfAMA-1 is processed to 66-kDa and then to 48- and 44-kDa products. We show that, even at low concentrations, IgG antibodies against correctly folded recombinant PfAMA-1 cross-linked and trapped the 52-, 48-, and 44-kDa proteolytic products on merozoites. These products are normally shed into the culture medium. At higher concentrations antibodies inhibited invasion into RBCs and caused a reduction in the amount of 44- and 48-kDa products, both on merozoites and in the culture medium. A corresponding increase also occurred in the amount of the 66- and 52-kDa forms detected on the merozoites. These antibodies also prevented circumferential redistribution of AMA-1. In contrast, monovalent invasion-inhibitory Fab fragments caused accumulation of 66- and 52-kDa forms, with no cross-linking, trapping, or prevention of redistribution. Antibodies at low concentrations can be used as trapping agents for intermediate and soluble forms of AMA-1 and are useful for studying proteolytic processing of AMA-1. With this technique, it was confirmed that protease inhibitor chymostatin and Ca2+ chelators can inhibit the breakdown of the 66-kDa form. We propose that antibodies to AMA-1 capable of inhibiting erythrocyte invasion act by disrupting proteolytic processing of AMA-1.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Anticorpos Antiprotozoários / Proteínas de Protozoários / Proteínas de Membrana / Antígenos de Protozoários Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Anticorpos Antiprotozoários / Proteínas de Protozoários / Proteínas de Membrana / Antígenos de Protozoários Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2003 Tipo de documento: Article País de afiliação: Estados Unidos