2019
DOI: 10.1128/msphere.00194-19
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Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the Plasmodium vivax Duffy Binding Protein Ligand Domain

Abstract: The Plasmodium vivax Duffy binding protein region II (DBPII) is a vital ligand for the parasite’s invasion of reticulocytes, thereby making this molecule an attractive vaccine candidate against vivax malaria. However, strain-specific immunity due to DBPII allelic variation in Bc epitopes may complicate vaccine efficacy, suggesting that an effective DBPII vaccine needs to target conserved epitopes that are potential targets of strain-transcending neutralizing immunity. The minimal epitopes reactive with functio… Show more

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Cited by 24 publications
(23 citation statements)
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“…The frequency of these SNPs was similar to this study, as in the case of Thailand [18], Myanmar [19], Sudan [21], and Papua New Guinea [17], or smaller as in the case of Sri-Lanka [22]. These data reinforce the idea that pvdbp-II diversity seems to occur independently of the malaria endemicity levels [23,24]. Further, eight SNPs were exclusively detected in AF, and, interestingly, two of them (K371N and E385Q/K) had been previously found in AF areas of Santa Catarina state [25].…”
Section: Discussionsupporting
confidence: 88%
“…The frequency of these SNPs was similar to this study, as in the case of Thailand [18], Myanmar [19], Sudan [21], and Papua New Guinea [17], or smaller as in the case of Sri-Lanka [22]. These data reinforce the idea that pvdbp-II diversity seems to occur independently of the malaria endemicity levels [23,24]. Further, eight SNPs were exclusively detected in AF, and, interestingly, two of them (K371N and E385Q/K) had been previously found in AF areas of Santa Catarina state [25].…”
Section: Discussionsupporting
confidence: 88%
“…In the case of P. vivax MSP1, antibody response to different regions of the protein appeared distinct, with the N-terminal portion predominantly associated with IgM antibodies and C-terminal with IgG response [54][55][56][57]. In the case of DBPII, several studies have mapped functional immunoreactive B cell epitopes associated with broadly neutralizing IgG antibody response [12,14,15,18], but no data is available about IgM response.…”
Section: Plos Onementioning
confidence: 99%
“…Duffy binding protein II (DBPII) is a leading P. vivax malaria vaccine candidate that binds the Duffy antigen receptor for chemokines (DARC) on reticulocytes is critical for reticulocyte invasion [9,10]. Although naturally acquired DBPII antibodies tend to be biased towards strain-specific responses [11][12][13], our project identified the epitope targets of protective neutralizing IgG antibody response to overlap conserved residues essential for receptor binding and DBP dimerization [12,[14][15][16][17][18][19]. Individuals able to produce these broadly binding-inhibitory antibodies (BIAb) to DBPII present reduced risk of clinical P. vivax malaria [20,21].…”
Section: Introductionmentioning
confidence: 99%
“…Clearly PvDBP has been the subject of decades of work, meaning that there are multiple lines of evidence supporting its candidacy. The limitations of this target are also well known, specifically the challenge of strain-specific antibody responses, which may be able to be overcome with epitope engineering (28,(66)(67)(68). One question in weighing up the candidacy of any vaccine antigen is whether the gene that encodes it is essential for parasite growth, as targeting a non-essential gene would seem likely to select for parasites that do not rely on the gene product, and so are able to escape the vaccine.…”
Section: Discussionmentioning
confidence: 99%