Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 588-596 |
Number of pages | 9 |
Journal | Haematologica |
Volume | 99 |
Issue number | 3 |
Early online date | 17 Jan 2014 |
DOIs | |
Publication status | Published - Mar 2014 |
Bibliographical note
Funding This work was supported by grants from the Scottish National Blood Transfusion Service and the Wellcome Trust, UK (058766).Keywords
- HLA-DR transgenic mice
- hemolytic disease of the newborn
- peptide therapy
- regulatory T cell
- RhD
Fingerprint
Dive into the research topics of 'Combination peptide immunotherapy suppresses antibody and helper T cell responses to the RhD protein in HLA-transgenic mice'. Together they form a unique fingerprint.Profiles
-
Mark Vickers
- 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