6R2S

The structure of Plasmodium vivax Duffy binding protein (PvDBP) bound to human antibody DB9

Summary for 6R2S

• Entry DOI: 10.2210/pdb6r2s/pdb
• Descriptor: Antibody DB9 light chain, Antibody DB9 heavy chain, Duffy receptor (3 entities in total)
• Functional Keywords: plasmodium vivax, invasion, broadly-neutralising human monoclonal antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 90563.67

Authors

Barber, N.M.,Higgins, M.K. (deposition date: 2019-03-18, release date: 2019-03-27, Last modification date: 2024-10-16)

Primary citation

Rawlinson, T.A.,Barber, N.M.,Mohring, F.,Cho, J.S.,Kosaisavee, V.,Gerard, S.F.,Alanine, D.G.W.,Labbe, G.M.,Elias, S.C.,Silk, S.E.,Quinkert, D.,Jin, J.,Marshall, J.M.,Payne, R.O.,Minassian, A.M.,Russell, B.,Renia, L.,Nosten, F.H.,Moon, R.W.,Higgins, M.K.,Draper, S.J.
Structural basis for inhibition of Plasmodium vivax invasion by a broadly neutralizing vaccine-induced human antibody.
Nat Microbiol, 4:1497-1507, 2019

PubMed Abstract: The most widespread form of malaria is caused by Plasmodium vivax. To replicate, this parasite must invade immature red blood cells through a process requiring interaction of the P. vivax Duffy binding protein (PvDBP) with its human receptor, the Duffy antigen receptor for chemokines. Naturally acquired antibodies that inhibit this interaction associate with clinical immunity, suggesting PvDBP as a leading candidate for inclusion in a vaccine to prevent malaria due to P. vivax. Here, we isolated a panel of monoclonal antibodies from human volunteers immunized in a clinical vaccine trial of PvDBP. We screened their ability to prevent PvDBP from binding to the Duffy antigen receptor for chemokines, and their capacity to block red blood cell invasion by a transgenic Plasmodium knowlesi parasite genetically modified to express PvDBP and to prevent reticulocyte invasion by multiple clinical isolates of P. vivax. This identified a broadly neutralizing human monoclonal antibody that inhibited invasion of all tested strains of P. vivax. Finally, we determined the structure of a complex of this antibody bound to PvDBP, indicating the molecular basis for inhibition. These findings will guide future vaccine design strategies and open up possibilities for testing the prophylactic use of such an antibody.

PubMed: 31133755
DOI: 10.1038/s41564-019-0462-1

Experimental method

X-RAY DIFFRACTION (3.04 Å)