CϵmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B cells (53.7)

Abstract Type-I hypersensitivity reactions play a critical role in the pathogenesis of various allergic diseases. The successful development of the anti-IgE antibody, omalizumab, has validated IgE as an effective therapeutic target for the treatment of various IgE-mediated allergic diseases. Two research groups have reported that mAbs specific for certain parts of CϵmX, a domain of 52 aa residues in human membrane-bound IgE (mIgE), can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC). Herein, we explore the virus-like particles (VLPs) formed by hepatitis B virus core antigen (HBcAg) that harbors the entire CϵmX peptide or its fragments as immunogens for inducing anti-CϵmX antibodies. Mice immunized subcutaneously with some of these immunogens produce antibodies that bind to recombinant CϵmX-containing human IgE.Fc in ELISA and Western blot analysis and to genetically engineered human mIgE-expressing Ramos B cell line in fluorescence flow cytometric assays. The IgG antibodies purified from the sera of immunized mice could cause the apoptosis of mIgE-expressing Ramos cells through a BCR-dependent caspase pathway. Furthermore, the IgG mediated ADCC on human mIgE-expressing murine B cell lymphoma A20. These results suggest that HBcAg-CϵmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases.