RESUMO
Different domains of a novel full-length var gene (termed 732var) isolated from a placenta of a malaria-infected woman were expressed in Escherichia coli as recombinant proteins and analysed biochemically and immunologically. Two of these, the Duffy binding-like (DBL)-3gamma domain and the cysteine-rich interdomain region (CIDR)-1alpha were able to bind chondroitin sulfate A and CD36, respectively. The DBL-3gamma domain was investigated in a previous study and confirmed here to exhibit anti-disease characteristics related to pregnancy-associated malaria. Mothers with high anti-DBL-3gamma antibody levels were protected from placental infection. The novel finding in this study is that babies born to mothers carrying anti-CIDR-1alpha antibodies had a delayed time to the first infection.
Assuntos
Antígenos de Protozoários/imunologia , Imunoglobulina G/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Complicações Parasitárias na Gravidez/imunologia , Proteínas de Protozoários/imunologia , Receptores de Superfície Celular/imunologia , Proteínas Recombinantes/imunologia , Adulto , Animais , Antígenos de Protozoários/química , Antígenos de Protozoários/genética , Antígenos de Protozoários/metabolismo , Antígenos CD36/metabolismo , Sulfatos de Condroitina/metabolismo , Sistema do Grupo Sanguíneo Duffy , Feminino , Humanos , Imunoglobulina G/sangue , Recém-Nascido , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Placenta , Gravidez , Complicações Parasitárias na Gravidez/parasitologia , Complicações Parasitárias na Gravidez/prevenção & controle , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
A recombinant Duffy binding-like (DBL)- gamma domain from a previously identified placental isolate, 732, was expressed by use of the baculovirus/insect cell system and was purified in milligram quantities. The recombinant protein binds specifically to chondroitin sulfate A (CSA) and inhibits CSA binding by placental infected erythrocytes (IEs). Polyclonal antibodies raised against the domain recognized the surfaces of live IEs from CSA-adherent clinical placental isolates. These antibodies also abrogated the in vitro binding of IEs to CSA. The 732 DBL-3 gamma domain was specifically recognized by plasma from pregnant women but not by plasma from control subjects. In addition, the protein was, comparatively, significantly more reactive with plasma from women with infected placentas, strongly suggesting that the 732 DBL-3 gamma domain carries preferentially IE-expressed immunogenic epitopes. High levels of plasma antibodies to the recombinant domain were associated with reduced placental parasite density. This is the first report of a recombinant DBL- gamma domain derived from a placental isolate that shows CSA-binding properties.