Combination peptide immunotherapy suppresses antibody and helper T cell responses to the RhD protein in HLA-transgenic mice

Lindsay S Hall, Andrew M Hall, Wendy Pickford, Mark A Vickers, Stanislaw J Urbaniak, Robert N Barker

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)588-596
Number of pages9
JournalHaematologica
Volume99
Issue number3
Early online date17 Jan 2014
DOIs
Publication statusPublished - 1 Mar 2014

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Keywords

  • HLA-DR transgenic mice
  • hemolytic disease of the newborn
  • peptide therapy
  • regulatory T cell
  • RhD

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