Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein

Brian T. Grimberg, Rachanee Udomsangpetch, Jia Xainli, Amy McHenry, Tasanee Panichakul, Jetsumon Sattabongkot, Liwang Cui, Moses Bockarie, Chetan Chitnis, John Adams, Peter A. Zimmerman, Christopher L. King

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Background: Plasmodium vivax invasion requires interaction between the human Duffy antigen on the surface of erythrocytes and the P. vivax Duffy binding protein (PvDBP) expressed by the parasite. Given that Duffy-negative individuals are resistant and that Duffy-negative heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized that antibodies directed against region two of P. vivax Duffy binding protein (PvDBPII) would inhibit P. vivax invasion of human erythrocytes. Methods and Findings: Using a recombinant region two of the P. vivax Duffy binding protein (rPvDBPII), polyclonal antibodies were generated from immunized rabbits and affinity purified from the pooled sera of 14 P. vivax-exposed Papua New Guineans. It was determined by ELISA and by flow cytometry, respectively, that both rabbit and human antibodies inhibited binding of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human erythrocytes. Additionally, using immunofluorescent microscopy, the antibodies were shown to attach to native PvDBP on the apical end of the P. vivax merozoite. In vitro invasion assays, using blood isolates from individuals in the Mae Sot district of Thailand, showed that addition of rabbit anti-PvDBPII Ab or serum (antibodies against, or serum containing antibodies against, region two of the Plasmodium vivax Duffy binding protein) (1:100) reduced the number of parasite invasions by up to 64%, while pooled PvDBPII antisera from P. vivax-exposed people reduced P. vivax invasion by up to 54%. Conclusions: These results show, for what we believe to be the first time, that both rabbit and human antibodies directed against PvDBPII reduce invasion efficiency of wild P. vivax isolated from infected patients, and suggest that a PvDBP-based vaccine may reduce human blood-stage P. vivax infection.

Original languageEnglish (US)
Pages (from-to)1940-1948
Number of pages9
JournalPLoS Medicine
Volume4
Issue number12
DOIs
StatePublished - Dec 1 2007

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Plasmodium vivax
Carrier Proteins
Erythrocytes
Antibodies
Blood
Rabbits
Antigens
Parasites
Serum
Flow cytometry
Merozoites
Immune Sera
Assays
Microscopic examination
Thailand
Surface Antigens
Heterozygote
Vaccines
Malaria
Plasmodium Duffy antigen binding protein

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Grimberg, B. T., Udomsangpetch, R., Xainli, J., McHenry, A., Panichakul, T., Sattabongkot, J., ... King, C. L. (2007). Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Medicine, 4(12), 1940-1948. https://doi.org/10.1371/journal.pmed.0040337
Grimberg, Brian T. ; Udomsangpetch, Rachanee ; Xainli, Jia ; McHenry, Amy ; Panichakul, Tasanee ; Sattabongkot, Jetsumon ; Cui, Liwang ; Bockarie, Moses ; Chitnis, Chetan ; Adams, John ; Zimmerman, Peter A. ; King, Christopher L. / Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. In: PLoS Medicine. 2007 ; Vol. 4, No. 12. pp. 1940-1948.
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title = "Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein",
abstract = "Background: Plasmodium vivax invasion requires interaction between the human Duffy antigen on the surface of erythrocytes and the P. vivax Duffy binding protein (PvDBP) expressed by the parasite. Given that Duffy-negative individuals are resistant and that Duffy-negative heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized that antibodies directed against region two of P. vivax Duffy binding protein (PvDBPII) would inhibit P. vivax invasion of human erythrocytes. Methods and Findings: Using a recombinant region two of the P. vivax Duffy binding protein (rPvDBPII), polyclonal antibodies were generated from immunized rabbits and affinity purified from the pooled sera of 14 P. vivax-exposed Papua New Guineans. It was determined by ELISA and by flow cytometry, respectively, that both rabbit and human antibodies inhibited binding of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human erythrocytes. Additionally, using immunofluorescent microscopy, the antibodies were shown to attach to native PvDBP on the apical end of the P. vivax merozoite. In vitro invasion assays, using blood isolates from individuals in the Mae Sot district of Thailand, showed that addition of rabbit anti-PvDBPII Ab or serum (antibodies against, or serum containing antibodies against, region two of the Plasmodium vivax Duffy binding protein) (1:100) reduced the number of parasite invasions by up to 64{\%}, while pooled PvDBPII antisera from P. vivax-exposed people reduced P. vivax invasion by up to 54{\%}. Conclusions: These results show, for what we believe to be the first time, that both rabbit and human antibodies directed against PvDBPII reduce invasion efficiency of wild P. vivax isolated from infected patients, and suggest that a PvDBP-based vaccine may reduce human blood-stage P. vivax infection.",
author = "Grimberg, {Brian T.} and Rachanee Udomsangpetch and Jia Xainli and Amy McHenry and Tasanee Panichakul and Jetsumon Sattabongkot and Liwang Cui and Moses Bockarie and Chetan Chitnis and John Adams and Zimmerman, {Peter A.} and King, {Christopher L.}",
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Grimberg, BT, Udomsangpetch, R, Xainli, J, McHenry, A, Panichakul, T, Sattabongkot, J, Cui, L, Bockarie, M, Chitnis, C, Adams, J, Zimmerman, PA & King, CL 2007, 'Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein', PLoS Medicine, vol. 4, no. 12, pp. 1940-1948. https://doi.org/10.1371/journal.pmed.0040337

Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. / Grimberg, Brian T.; Udomsangpetch, Rachanee; Xainli, Jia; McHenry, Amy; Panichakul, Tasanee; Sattabongkot, Jetsumon; Cui, Liwang; Bockarie, Moses; Chitnis, Chetan; Adams, John; Zimmerman, Peter A.; King, Christopher L.

In: PLoS Medicine, Vol. 4, No. 12, 01.12.2007, p. 1940-1948.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein

AU - Grimberg, Brian T.

AU - Udomsangpetch, Rachanee

AU - Xainli, Jia

AU - McHenry, Amy

AU - Panichakul, Tasanee

AU - Sattabongkot, Jetsumon

AU - Cui, Liwang

AU - Bockarie, Moses

AU - Chitnis, Chetan

AU - Adams, John

AU - Zimmerman, Peter A.

AU - King, Christopher L.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - Background: Plasmodium vivax invasion requires interaction between the human Duffy antigen on the surface of erythrocytes and the P. vivax Duffy binding protein (PvDBP) expressed by the parasite. Given that Duffy-negative individuals are resistant and that Duffy-negative heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized that antibodies directed against region two of P. vivax Duffy binding protein (PvDBPII) would inhibit P. vivax invasion of human erythrocytes. Methods and Findings: Using a recombinant region two of the P. vivax Duffy binding protein (rPvDBPII), polyclonal antibodies were generated from immunized rabbits and affinity purified from the pooled sera of 14 P. vivax-exposed Papua New Guineans. It was determined by ELISA and by flow cytometry, respectively, that both rabbit and human antibodies inhibited binding of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human erythrocytes. Additionally, using immunofluorescent microscopy, the antibodies were shown to attach to native PvDBP on the apical end of the P. vivax merozoite. In vitro invasion assays, using blood isolates from individuals in the Mae Sot district of Thailand, showed that addition of rabbit anti-PvDBPII Ab or serum (antibodies against, or serum containing antibodies against, region two of the Plasmodium vivax Duffy binding protein) (1:100) reduced the number of parasite invasions by up to 64%, while pooled PvDBPII antisera from P. vivax-exposed people reduced P. vivax invasion by up to 54%. Conclusions: These results show, for what we believe to be the first time, that both rabbit and human antibodies directed against PvDBPII reduce invasion efficiency of wild P. vivax isolated from infected patients, and suggest that a PvDBP-based vaccine may reduce human blood-stage P. vivax infection.

AB - Background: Plasmodium vivax invasion requires interaction between the human Duffy antigen on the surface of erythrocytes and the P. vivax Duffy binding protein (PvDBP) expressed by the parasite. Given that Duffy-negative individuals are resistant and that Duffy-negative heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized that antibodies directed against region two of P. vivax Duffy binding protein (PvDBPII) would inhibit P. vivax invasion of human erythrocytes. Methods and Findings: Using a recombinant region two of the P. vivax Duffy binding protein (rPvDBPII), polyclonal antibodies were generated from immunized rabbits and affinity purified from the pooled sera of 14 P. vivax-exposed Papua New Guineans. It was determined by ELISA and by flow cytometry, respectively, that both rabbit and human antibodies inhibited binding of rPvDBPII to the Duffy antigen N-terminal region and to Duffy-positive human erythrocytes. Additionally, using immunofluorescent microscopy, the antibodies were shown to attach to native PvDBP on the apical end of the P. vivax merozoite. In vitro invasion assays, using blood isolates from individuals in the Mae Sot district of Thailand, showed that addition of rabbit anti-PvDBPII Ab or serum (antibodies against, or serum containing antibodies against, region two of the Plasmodium vivax Duffy binding protein) (1:100) reduced the number of parasite invasions by up to 64%, while pooled PvDBPII antisera from P. vivax-exposed people reduced P. vivax invasion by up to 54%. Conclusions: These results show, for what we believe to be the first time, that both rabbit and human antibodies directed against PvDBPII reduce invasion efficiency of wild P. vivax isolated from infected patients, and suggest that a PvDBP-based vaccine may reduce human blood-stage P. vivax infection.

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Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J et al. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Medicine. 2007 Dec 1;4(12):1940-1948. https://doi.org/10.1371/journal.pmed.0040337