Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein.
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 su...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-12-01
|
| Series: | PLoS Medicine |
| Online Access: | http://europepmc.org/articles/PMC2140086?pdf=render |
| _version_ | 1811228466629050368 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Brian T Grimberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:58:23Z |
| format | Article |
| id | doaj.art-25a0096712094da4bdaf6c0a82c1397d |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-04-12T09:58:23Z |
| publishDate | 2007-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-25a0096712094da4bdaf6c0a82c1397d2022-12-22T03:37:37ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762007-12-01412e33710.1371/journal.pmed.0040337Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein.Brian T GrimbergRachanee UdomsangpetchJia XainliAmy McHenryTasanee PanichakulJetsumon SattabongkotLiwang CuiMoses BockarieChetan ChitnisJohn AdamsPeter A ZimmermanChristopher L KingBACKGROUND: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.http://europepmc.org/articles/PMC2140086?pdf=render |
| spellingShingle | 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 Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Medicine |
| title | Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. |
| title_full | Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. |
| title_fullStr | Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. |
| title_full_unstemmed | Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. |
| title_short | Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. |
| title_sort | plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the duffy binding protein |
| url | http://europepmc.org/articles/PMC2140086?pdf=render |
| work_keys_str_mv | AT briantgrimberg plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT rachaneeudomsangpetch plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT jiaxainli plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT amymchenry plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT tasaneepanichakul plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT jetsumonsattabongkot plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT liwangcui plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT mosesbockarie plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT chetanchitnis plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT johnadams plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT peterazimmerman plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein AT christopherlking plasmodiumvivaxinvasionofhumanerythrocytesinhibitedbyantibodiesdirectedagainsttheduffybindingprotein |