The offspring from pregnancies of women who have developed anti-D blood group antibodies are at risk of hemolytic disease of the newborn. We have previously mapped four peptides containing immunodominant T-helper cell epitopes from the RhD protein and the purpose of the work was to develop these into a product for suppression of established anti-D responses. A panel of each of the four immunodominant RhD peptides was synthesized with modifications to improve manufacturability and solubility, and screened for retention of recognition by human T-helper cells. A selected version of each sequence was combined in a mixture (RhDPmix), which was tested for suppressive ability in a humanized murine model of established immune responses to RhD protein. After HLA-DR15 transgenic mice had been immunized with RhD protein, a single dose of RhDPmix, given either intranasally (p=0.008, Mann-Whitney rank sum test) or subcutaneously (p=0.043), rapidly and significantly suppressed the ongoing antibody response. This was accompanied by reduced T-helper cell responsiveness, although this change was less marked for subcutaneous RhDPmix delivery, and by the recruitment of cells with a regulatory T-cell phenotype. The results support human trials of RhDPmix peptide immunotherapy in women with established antibody responses to the RhD blood group.
Bibliographical noteFunding This work was supported by grants from the Scottish National Blood Transfusion Service and the Wellcome Trust, UK (058766).
- HLA-DR transgenic mice
- hemolytic disease of the newborn
- peptide therapy
- regulatory T cell
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- School of Medicine, Medical Sciences & Nutrition, Microbiology and Immunity
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cancer Centre
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Applied Medicine (Clin)
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Clinical Academic