Duffy antigen is expressed during erythropoiesis in Duffy-negative individuals

Dechavanne, Celia; Dechavanne, Sebastien; Bosch, Jürgen; Metral, Sylvain; Redinger, Karli R.; Watson, Quentin D.; Ratsimbasoa, Arsene C.; Roeper, Brooke; Krishnan, Sushma; Fong, Rich; Bennett, Seth; Carias, Lenore; Chen, Edwin; Salinas, Nichole D.; Ghosh, Anil; Tolia, Niraj H.; Woost, Philip G.; Jacobberger, James W.; Colin, Yves; Gamain, Benoit; King, Christopher L.; Zimmerman, Peter A.

doi:10.1016/j.chom.2023.10.019

Cited by 9 publications

(3 citation statements)

References 86 publications

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“…These cases generally show lower parasitaemia and may thus contribute to the undetected low-transmission reservoir in Africa [39]. Very recently, two investigations could show the existence of a subset of Fy a-/b- erythroblasts that transiently express DARC and can be infected by Pv , thus providing a scientific reasoning behind the transmission of Pv infection in Duffy negative individuals [40,41]. With the Pv invasion pathway so reliant on the specific DARC genotype, it could be speculated that this may also have a significant effect on Pk GIA results.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Precision of thePlasmodium knowlesiGrowth Inhibition Assay forPlasmodium vivaxDuffy-Binding Protein-based Malaria Vaccine Development

Mertens,

Rigby,

Bardelli

et al. 2024

Preprint

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Recent data indicate increasing disease burden and importance ofPlasmodium vivax(Pv) malaria. A robust assay will be essential for blood-stagePvvaccine development. Results of thein vitrogrowth inhibition assay (GIA) with transgenicP. knowlesi(Pk) parasites expressing thePvDuffy-binding protein region II (PvDBPII) correlate within vivoprotection in the firstPvDBPII con-trolled human malaria infection (CHMI) trials, making thePkGIA an ideal selection tool once the precision of the assay is defined. To determine the precision in percentage of inhibition in GIA (%GIA) and in GIA50(antibody concentration that gave 50 %GIA), ten GIAs with transgenicPkparasites were conducted evaluating four different anti-PvDBPII human monoclonal antibodies (mAbs) at different concentrations, and three GIAs were conducted testing eighty anti-PvDBPII human polyclonal antibodies (pAbs) at 10 mg/mL. A significant assay-to-assay variation was observed, and the analysis revealed a standard deviation (SD) of 13.1 in the mAb and 5.94 in the pAb dataset for %GIA, with a LogGIA50SD of 0.299 (for mAbs). Moreover, the ninety-five percent confidence interval (95%CI) for %GIA or GIA50in repeat assays was calculated in this investigation. These results will support the development of future blood-stage malaria vaccines, specifically second generationPvDBPII-based formulations.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Precision of thePlasmodium knowlesiGrowth Inhibition Assay forPlasmodium vivaxDuffy-Binding Protein-based Malaria Vaccine Development

Mertens,

Rigby,

Bardelli

et al. 2024

Preprint

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“…As we look to the future, P. vivax must be in our sights for vaccines for African children who are DARC-negative. Recently, two studies have shown that a subpopulation of red blood cell progenitor is expressing low level of DARC and was invaded by P. vivax ( 43 – 45 ). However, it is still unknown whether DARC is a receptor for P. vivax infection of DARC-negative people in Africa or whether PvDBP-RII can be a vaccine for DARC-negative people.…”

Section: Discussionmentioning

confidence: 99%

Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein

Lee,

Crosnier,

Valenzuela-Leon

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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The discovery that Africans were resistant to infection by Plasmodium vivax ( P. vivax ) led to the conclusion that P. vivax invasion relied on the P. vivax Duffy Binding Protein (PvDBP) interacting with the Duffy Antigen Receptor for Chemokines (DARC) expressed on erythrocytes. However, the recent reporting of P. vivax infections in DARC-negative Africans suggests that the parasite might use an alternate invasion pathway to infect DARC-negative reticulocytes. To identify the parasite ligands and erythrocyte receptors that enable P. vivax invasion of both DARC-positive and -negative erythrocytes, we expressed region II containing the Duffy Binding-Like (DBL) domain of P. vivax erythrocyte binding protein (PvEBP-RII) and verified that the DBL domain binds to both DARC-positive and -negative erythrocytes. Furthermore, an AVidity-based EXtracelluar Interaction Screening (AVEXIS) was used to identify the receptor for PvEBP among over 750 human cell surface receptor proteins, and this approach identified only Complement Receptor 1 (CR1, CD35, or C3b/C4b receptor) as a PvEBP receptor. CR1 is a well-known receptor for P. falciparum Reticulocyte binding protein Homology 4 (PfRh4) and is present on the surfaces of both reticulocytes and normocytes, but its expression decreases as erythrocytes age. Indeed, PvEBP-RII bound to a subpopulation of both reticulocytes and normocytes, and this binding was blocked by the addition of soluble CR1 recombinant protein, indicating that CR1 is the receptor of PvEBP. In addition, we found that the Long Homology Repeat A (LHR-A) subdomain of CR1 is the only subdomain responsible for mediating the interaction with PvEBP-RII.

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“…Genetic variation in DARC resulted in the designation of Duffy‐negative individuals who were initially thought to lack DARC expression on red cells conferring protection from P. vivax (Miller et al, 1976 ). Recent data have demonstrated that Duffy‐negativity is a misnomer and the genetic differences in the DARC locus result in reduced but present expression of DARC thereby resulting in moderate protection against infection (Bouyssou et al, 2023 ; Dechavanne et al, 2023 ). These results establish the DBP:DARC interaction as a key target for interventions leading to protection for all individuals regardless of DARC status (Duffy et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Structure‐based design of a Plasmodium vivax Duffy‐binding protein immunogen focuses the antibody response to functional epitopes

Dickey,

McAleese,

Salinas

et al. 2024

Protein Science

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The Duffy‐binding protein (DBP) is a promising antigen for a malaria vaccine that would protect against clinical symptoms caused by Plasmodium vivax infection. Region II of DBP (DBP‐II) contains the receptor‐binding domain that engages host red blood cells, but DBP‐II vaccines elicit many non‐neutralizing antibodies that bind distal to the receptor‐binding surface. Here, we engineered a truncated DBP‐II immunogen that focuses the immune response to the receptor‐binding surface. This immunogen contains the receptor‐binding subdomain S1S2 and lacks the immunodominant subdomain S3. Structure‐based computational design of S1S2 identified combinatorial amino acid changes that stabilized the isolated S1S2 without perturbing neutralizing epitopes. This immunogen elicited DBP‐II‐specific antibodies in immunized mice that were significantly enriched for blocking activity compared to the native DBP‐II antigen. This generalizable design process successfully stabilized an integral core fragment of a protein and focused the immune response to desired epitopes to create a promising new antigen for malaria vaccine development.

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Duffy antigen is expressed during erythropoiesis in Duffy-negative individuals

Cited by 9 publications

References 86 publications

Evaluation of Precision of thePlasmodium knowlesiGrowth Inhibition Assay forPlasmodium vivaxDuffy-Binding Protein-based Malaria Vaccine Development

Evaluation of Precision of thePlasmodium knowlesiGrowth Inhibition Assay forPlasmodium vivaxDuffy-Binding Protein-based Malaria Vaccine Development

Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein

Structure‐based design of a Plasmodium vivax Duffy‐binding protein immunogen focuses the antibody response to functional epitopes

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