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1.
Infect Immun ; 70(6): 2772-9, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12010962

RESUMEN

The 42-kDa carboxyl-terminal processing fragment of Plasmodium falciparum merozoite surface protein 1 (MSP-1(42)) is an anti-erythrocytic stage malaria vaccine candidate. In this study, MSP-1(42) was expressed by using the Bombyx mori nuclear polyhedrosis virus-silkworm expression system, and the antigenicity and immmunogenicity of the recombinant protein, Bmp42, were evaluated. The average yield of Bmp42, as determined by a sandwich enzyme-linked immunosorbent assay (ELISA), was 379 microg/ml of infected silkworm hemolymph, which was >100-fold higher than the level attainable in cell culture medium. N-terminal amino acid sequencing revealed that Bmp42 was correctly processed in silkworm cells. Data from immunoblotting, as well as from the inhibition ELISA, suggested that the conformational B-cell epitopes of MSP-1(42) were recreated in Bmp42. Immunization of rabbits with Bmp42 in complete Freund's adjuvant generated high-titer antibody responses against the immunogen. Specificity analyses of the anti-Bmp42 antibodies using several recombinant MSP-1(19) proteins expressing variant and conserved B-cell epitopes suggested that the anti-Bmp42 antibodies recognized primarily conserved epitopes on MSP-1(19). Furthermore, the anti-Bmp42 antibodies were highly effective in inhibiting the in vitro growth of parasites carrying homologous or heterologous MSP-1(42). Our results demonstrated that the baculovirus-silkworm expression system could be employed to express biologically and immunologically active recombinant MSP-1(42) at elevated levels; thus, it is an attractive alternative for producing a protective MSP-1(42) vaccine for human use.


Asunto(s)
Expresión Génica , Vectores Genéticos , Proteína 1 de Superficie de Merozoito/genética , Nucleopoliedrovirus , Plasmodium falciparum/genética , Procesamiento Proteico-Postraduccional , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Bombyx , Línea Celular , Larva , Proteína 1 de Superficie de Merozoito/inmunología , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Plasmodium falciparum/inmunología , Conejos , Análisis de Secuencia de Proteína , Vacunas Sintéticas/inmunología
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