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.
Highlights
Plasmodium vivax is a cause of morbidity and mortality in Thailand and other countries in South East Asia and worldwide about three billion people live at risk of infection by P. vivax [1,2]
Duffy binding protein (DBP) is the product of a single copy gene and is a member of the Duffy binding-like erythrocyte binding protein family (DBL-EBP) family, which are expressed in the micronemes and on the surface of P. vivax merozoites, and is associated with the decisive junction formation step during the invasion process [8]
Acquired responses to total (PvSE) and Duffy binding protein region II (DBPII) To assess the immunological responses during P. vivax infection, the reactivity of naturally acquired antibodies were tested against crude schizont antigen (PvSE) and the vaccine candidate DBPII
Summary
Plasmodium vivax is a cause of morbidity and mortality in Thailand and other countries in South East Asia and worldwide about three billion people live at risk of infection by P. vivax [1,2]. DBP is the product of a single copy gene and is a member of the Duffy binding-like erythrocyte binding protein family (DBL-EBP) family, which are expressed in the micronemes and on the surface of P. vivax merozoites, and is associated with the decisive junction formation step during the invasion process [8]. It is this critical interaction of DBP with its cognate receptor DARC that makes DBP an important anti-vivax vaccine candidate
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