Induction of strain-transcendent antibodies to placental-type isolates with VAR2CSA DBL3 or DBL5 recombinant proteins

Malaria Journal

Research

Megan M Cartwright¹  Marianne J Hathaway¹  Marion Avril¹  Joseph D Smith² 

[1] Seattle Biomedical Research Institute, 307 Westlake Ave N, Suite 500, 98109-5219, Seattle Washington, USA;Seattle Biomedical Research Institute, 307 Westlake Ave N, Suite 500, 98109-5219, Seattle Washington, USA;Department of Global Health, University of Washington, 98195, Seattle, WA, USA;

关键词: Malaria;    Recombinant Protein;    Pichia Pastoris;    Infected Erythrocyte;    Parasite Line;   

DOI  :  10.1186/1475-2875-10-36

 received in 2010-12-16, accepted in 2011-02-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundPregnancy associated malaria is a severe clinical syndrome associated with sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, which adheres to chondroitin sulphate A (CSA). VAR2CSA is a large and polymorphic protein that has six Duffy binding-like (DBL) domains. There is still limited understanding as to how effective individual VAR2CSA domains are at generating inhibitory antibodies or the number of domain variants needed for universal vaccine coverage.MethodsTo investigate the immunogenic properties of single domain VAR2CSA recombinant proteins, rats or rabbits were immunized with five of the six VAR2CSA domains produced in Pichia pastoris. Immune plasma was analysed against a geographically diverse panel of CSA-binding lab lines to assess antibody breadth and inhibitory activity.ResultsOf the five domains, DBL3, and to a lesser extent DBL5, induced antibodies that cross-reacted on five diverse CSA-binding parasite lines by flow cytometry. By comparison, anti-DBL6 antibodies were highly strain-specific and anti-DBL1 and anti-DBL4 antibodies were poorly reactive by flow cytometry. From this series of recombinant proteins, adhesion-blocking activity was restricted to a single rat immunized against a DBL4 recombinant protein.ConclusionsSingle domain VAR2CSA recombinant proteins produced in P. pastoris had limited efficacy in eliciting adhesion blocking antibody responses, but VAR2CSA DBL3 and DBL5 domains contain strain-transcendent epitopes that can be targeted by vaccination and may have application for vaccine development.

【 授权许可】

Unknown   
© Avril et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.