a conserved multi-gene family induces cross-reactive antibodies effective in defense against plasmodium falciparum守恒的多基因家族诱发可交叉反应的抗体有效地对抗恶性疟原虫.pdfVIP

A Conserved Multi-Gene Family Induces Cross-Reactive Antibodies Effective in Defense against Plasmodium falciparum 1¤ 1 1 2 ´ 1 Subhash Singh *, Soe Soe , Simon Weisman , John W. Barnwell , Jean Louis Perignon , Pierre Druilhe1* 1 Bio-medical Parasitology Unit, Institut Pasteur, Paris, France, 2 Malaria Branch, Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Abstract Background: Two related merozoite surface proteins, MSP3 and MSP6, have previously been identified as targets of antibody-dependent cellular inhibition (ADCI), a protective mechanism against Plasmodium falciparum malaria. Both MSP3 and MSP6 share a common characteristic small N-terminal signature amino-acid stretch (NLRNA/G), a feature similar to MSP3-like orthologs identified in other human and primate malaria parasites. Methods/Results: This signature amino-acid sequence led to the identification of eight ORFs contiguously located on P. falciparum chromosome 10. Our subsequent investigations on their expression, localization, sequence conservation, epitope sharing, immunogenicity and the functional role of antibodies in defense are reported here. Six members of P. falciparum MSP3-multigene family share similar sequence organization within their C-terminal regions, are simultaneously expressed as merozoite surface proteins and are highly conserved among parasite isolates. Each of these proteins is a target of naturally occurring antibodies effective at parasite killing in ADCI assays. Moreover, both naturally occurring antibodies and those generated by immunization display cross-reactivity with other members of the family and exhibit varied binding avi