A PVDBP monoclonal antibody recognizes a conserved epitope in Plasmodium falciparum and P. chabaudi antigens
Year: 2017
Type: conference-paper
Abstract: The Plasmodium falciparum parasite has evolved numerous adaptations to survive in its human host. A key adaptation is the cytoadherence of infected erythrocytes (IE) to host tissues, allowing the parasite to escape detection by the immune system and resulting in the significant pathologies associated with malaria. In pregnancy, P. falciparum expresses the protein VAR2CSA on the surface of IEs, which allows the parasite to adhere to chondroitin sulfate A (CSA) expressed on the surface of the placenta. In Africa, where P. falciparum is holoendemic, antibodies to VAR2CSA are acquired through successive exposure to P. falciparum in pregnancy and are able to protect the mother and child by blocking parasite adhesion to CSA. Recently, we discovered a novel mechanism for protection against malaria in pregnancy through exposure to a surface protein from P. vivax that is structurally related to VAR2CSA. We found that a monoclonal antibody (mAb) against the P. vivax protein, PvDBP, recognized VAR2CSA through shared DBL domains. Here, using live and fixed CS2 IEs, we show that there is partial overlap between the recognition sites of a polyclonal antibody against VAR2CSA and the PvDBP mAb. In addition, prior incubation of IE with the VAR2CSA antibody did not block recognition by the PvDBP mAb, suggesting there are epitopes, possibly cryptic, that are exclusively recognized by the mAb. We further show that cross-recognition extends beyond VAR2CSA. As demonstrated by flow cytometry, the PvDBP mAb recognized a significant proportion of unselected 3D7 IEs. Lastly, using ELISA and western blot methods, we found that the mAb recognized a recombinant protein from the murine malaria parasite P. chabaudi, which we identified based on sequence homology with PvDBP. These results suggest that there is a highly conserved epitope in proteins expressed by several species in the Plasmodium genus, which could offer important insight into malaria immunity and for vaccine development.
Source: Griffith Research Online
Authors: Mitran, Catherine J, Banman, Shanna, Gnidehou, Sedami, Taylor, Brian, Rieger, Aja M, Ntumngia, Francis, Adams, John H, Good, Michael F, Yanow, Stephanie K
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7024414889