Vivax malaria and Duffy antigen: Stop being so negative

Duffy, Patrick E.; Gunalan, Karthigayan; Miller, Louis H.

doi:10.1016/j.chom.2023.11.017

Cited by 6 publications

(1 citation statement)

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“…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: 54%

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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Section: Introductionmentioning

confidence: 54%