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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/2067
Title: Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand
Authors: Patchanee Chootong
Tasanee Panichakul
Chongrak Permmongkol
Samantha J. Barnes
Rachanee Udomsangpetch
John H. Adams
Department of Clinical Microbiology and Applied Technology
Keywords: Anti-Duffy Binding Protein;plasmodium vivax Vaccine;Thailand
Issue Date: Apr-2012
Publisher: Mahidol University
Citation: Plos One. Vol.7, No.4 (2012), e35769
Abstract: Plasmodium vivax Duffy binding protein region II (DBPII) is an important vaccine candidate for antibody-mediated immunity against vivax malaria. A significant challenge for vaccine development of DBPII is its highly polymorphic nature that alters sensitivity to neutralizing antibody responses. Here, we aim to characterize naturally-acquired neutralizing antibodies against DBPII in individual Thai residents to give insight into P. vivax vaccine development in Thailand. Anti-DBPII IgG significantly increased in acute vivax infections compared to uninfected residents and naive controls. Antibody titers and functional anti-DBPII inhibition varied widely and there was no association between titer and inhibition activity. Most high titer plasmas had only a moderate to no functional inhibitory effect on DBP binding to erythrocytes, indicating the protective immunity against DBPII binding is strain specific. Only 5 of 54 samples were highly inhibitory against DBP erythrocyte-binding function. Previously identified target epitopes of inhibitory anti-DBPPII IgG (H1, H2 and H3) were localized to the dimer interface that forms the DARC binding pocket. Amino acid polymorphisms (monomorphic or dimorphic) in H1 and H3 protective epitopes change sensitivity of immune inhibition by alteration of neutralizing antibody recognition. The present study indicates Thai variant H1.T1 (R308S), H3.T1 (D384G) and H3.T3 (K386N) are the most important variants for a DBPII candidate vaccine needed to protect P. vivax in Thai residents.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/2067
metadata.dc.identifier.url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338783/pdf/pone.0035769.pdf
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