Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> 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 ma...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-06-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00194-19 |
| _version_ | 1819041666079653888 |
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| author | Miriam T. George Jesse L. Schloegel Francis B. Ntumngia Samantha J. Barnes Christopher L. King Joanne L. Casey Michael Foley John H. Adams |
| author_facet | Miriam T. George Jesse L. Schloegel Francis B. Ntumngia Samantha J. Barnes Christopher L. King Joanne L. Casey Michael Foley John H. Adams |
| author_sort | Miriam T. George |
| collection | DOAJ |
| description | 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 functionally inhibitory anti-DBPII monoclonal antibody (MAb) 3C9 and noninhibitory anti-DBPII MAb 3D10 were mapped using phage display expression libraries, since previous attempts to deduce the 3C9 epitope by cocrystallographic methods failed. Inhibitory MAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3, while noninhibitory MAb 3D10 binds to a linear epitope in subdomain 1 of DBPII, consistent with previous studies. Immunogenicity studies using synthetic linear peptides of the minimal epitopes determined that the 3C9 epitope, but not the 3D10 epitope, could induce functionally inhibitory anti-DBPII antibodies. Therefore, the highly conserved binding-inhibitory 3C9 epitope offers the potential as a component in a broadly inhibitory, strain-transcending DBP subunit vaccine. IMPORTANCE Vivax malaria is the second leading cause of malaria worldwide and the major cause of non-African malaria. Unfortunately, efforts to develop antimalarial vaccines specifically targeting Plasmodium vivax have been largely neglected, and few candidates have progressed into clinical trials. The Duffy binding protein is considered a leading blood-stage vaccine candidate because this ligand’s recognition of the Duffy blood group reticulocyte surface receptor is considered essential for infection. This study identifies a new target epitope on the ligand’s surface that may serve as the target of vaccine-induced binding-inhibitory antibody (BIAb). Understanding the potential targets of vaccine protection will be important for development of an effective vaccine. |
| first_indexed | 2024-12-21T09:28:37Z |
| format | Article |
| id | doaj.art-7d160bd61e2246ffac628b8c97927e47 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-21T09:28:37Z |
| publishDate | 2019-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-7d160bd61e2246ffac628b8c97927e472022-12-21T19:08:49ZengAmerican Society for MicrobiologymSphere2379-50422019-06-014310.1128/mSphere.00194-19Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand DomainMiriam T. George0Jesse L. Schloegel1Francis B. Ntumngia2Samantha J. Barnes3Christopher L. King4Joanne L. Casey5Michael Foley6John H. Adams7Center for Global Health and Infectious Disease Research, Department of Global Health, University of South Florida, Tampa, Florida, USACenter for Global Health and Infectious Disease Research, Department of Global Health, University of South Florida, Tampa, Florida, USACenter for Global Health and Infectious Disease Research, Department of Global Health, University of South Florida, Tampa, Florida, USACenter for Global Health and Infectious Disease Research, Department of Global Health, University of South Florida, Tampa, Florida, USACenter for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USADepartment of Biochemistry, La Trobe University, Melbourne, Victoria, AustraliaDepartment of Biochemistry, La Trobe University, Melbourne, Victoria, AustraliaCenter for Global Health and Infectious Disease Research, Department of Global Health, University of South Florida, Tampa, Florida, USAABSTRACT 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 functionally inhibitory anti-DBPII monoclonal antibody (MAb) 3C9 and noninhibitory anti-DBPII MAb 3D10 were mapped using phage display expression libraries, since previous attempts to deduce the 3C9 epitope by cocrystallographic methods failed. Inhibitory MAb 3C9 binds to a conserved conformation-dependent epitope in subdomain 3, while noninhibitory MAb 3D10 binds to a linear epitope in subdomain 1 of DBPII, consistent with previous studies. Immunogenicity studies using synthetic linear peptides of the minimal epitopes determined that the 3C9 epitope, but not the 3D10 epitope, could induce functionally inhibitory anti-DBPII antibodies. Therefore, the highly conserved binding-inhibitory 3C9 epitope offers the potential as a component in a broadly inhibitory, strain-transcending DBP subunit vaccine. IMPORTANCE Vivax malaria is the second leading cause of malaria worldwide and the major cause of non-African malaria. Unfortunately, efforts to develop antimalarial vaccines specifically targeting Plasmodium vivax have been largely neglected, and few candidates have progressed into clinical trials. The Duffy binding protein is considered a leading blood-stage vaccine candidate because this ligand’s recognition of the Duffy blood group reticulocyte surface receptor is considered essential for infection. This study identifies a new target epitope on the ligand’s surface that may serve as the target of vaccine-induced binding-inhibitory antibody (BIAb). Understanding the potential targets of vaccine protection will be important for development of an effective vaccine.https://journals.asm.org/doi/10.1128/mSphere.00194-19DBPIIPlasmodium vivaxepitope mappingmalariavaccine |
| spellingShingle | Miriam T. George Jesse L. Schloegel Francis B. Ntumngia Samantha J. Barnes Christopher L. King Joanne L. Casey Michael Foley John H. Adams Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain mSphere DBPII Plasmodium vivax epitope mapping malaria vaccine |
| title | Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain |
| title_full | Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain |
| title_fullStr | Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain |
| title_full_unstemmed | Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain |
| title_short | Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the <named-content content-type="genus-species">Plasmodium vivax</named-content> Duffy Binding Protein Ligand Domain |
| title_sort | identification of an immunogenic broadly inhibitory surface epitope of the named content content type genus species plasmodium vivax named content duffy binding protein ligand domain |
| topic | DBPII Plasmodium vivax epitope mapping malaria vaccine |
| url | https://journals.asm.org/doi/10.1128/mSphere.00194-19 |
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