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Immunization with PfEMP1-DBL1alpha generates antibodies that disrupt rosettes and protect against the sequestration of Plasmodium falciparum-infected erythrocytes.

Abstract：

:A family of parasite antigens known as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is believed to play an important role in the binding of infected erythrocytes to host receptors in the micro-vasculature. Available data advocates the existence of a subset of very adhesive (rosetting, auto-agglutinating) and antigenic PfEMP1s implicated as virulence factors. Serum antibodies that disrupt rosettes are rarely found in children with severe malaria but are frequent in those with mild disease suggesting that they may be protective. Here we have developed a Semliki forest virus (SFV) vaccine construct with a recombinant gene (mini-var gene) encoding a mini-PfEMP1 (DBL1alpha-TM-ATS) obtained from a particularly antigenic and rosetting parasite (FCR3S1.2). The mini-PfEMP1 is presented to the host mimicking the location of the native molecule at the infected erythrocyte surface. Antibodies generated by a regimen of priming with SFV RNA particles and boosting with a recombinant protein recognize the infected erythrocyte surface (immuno-fluorescence/rosette-disruption) and prevent the sequestration of P. falciparum-infected erythrocytes in an in vivo model of severe malaria. The data prove the involvement of DBL1alpha in the adhesion of infected- and uninfected erythrocytes and the role of rosette-disruptive antibodies in preventing these cellular interactions. The work supports the use of DBL1alpha in a vaccine again severe malaria.

journal_name

Vaccine

journal_title

Vaccine

authors

Chen Q,Pettersson F,Vogt AM,Schmidt B,Ahuja S,Liljeström P,Wahlgren M

doi

10.1016/j.vaccine.2004.02.015

subject

Has Abstract

pub_date

2004-07-29 00:00:00

pages

2701-12

issue

21-22

eissn

0264-410X

issn

1873-2518

pii

S0264410X04001355

journal_volume

22

pub_type

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