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

Vaccine
Qijun ChenMats Wahlgren

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 ...Continue Reading

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Citations

Sep 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Johan NormarkMats Wahlgren
Apr 3, 2014·Cellular and Molecular Life Sciences : CMLS·Jo-Anne ChanJames G Beeson
Jun 9, 2005·The Journal of Experimental Medicine·Gerhard WinterMats Wahlgren
Oct 22, 2005·Infection and Immunity·Fredrik PetterssonMats Wahlgren
Oct 3, 2006·PLoS Pathogens·Anna M VogtMats Wahlgren
Oct 9, 2009·Current Opinion in Hematology·J Alexandra RoweThomas N Williams
Sep 8, 2010·Expert Review of Anti-infective Therapy·Chandy C JohnRobert O Opoka
Mar 8, 2008·Expert Review of Vaccines·Johan Vekemans, W Ripley Ballou
Nov 28, 2008·Trends in Parasitology·Carmen Fernandez-BecerraHernando A del Portillo
Aug 21, 2009·Parasite Immunology·K J Limbach, T L Richie
Feb 2, 2006·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Annelies Riezebos-BrilmanToos Daemen
Oct 19, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ernest MolesXavier Fernàndez-Busquets
Oct 19, 2006·Vaccine·Marc P GirardMarie Paule Kieny
May 17, 2017·The Korean Journal of Parasitology·Ui-Han SonYoun-Kyoung Goo
Aug 30, 2005·Anais Da Academia Brasileira De Ciências·Karin Kirchgatter, Hernando A Del Portillo
Aug 18, 2006·Vaccine·Shengqiang LiFilip Dubovsky
Oct 2, 2014·Expert Review of Vaccines·Karl Ljungberg, Peter Liljeström
Jun 13, 2017·Nature Reviews. Microbiology·Mats WahlgrenReetesh R Akhouri
Mar 29, 2006·Current Opinion in Hematology·Rick M Fairhurst, Thomas E Wellems
Sep 18, 2021·Expert Review of Vaccines·D Herbert OpiJames G Beeson

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