A Fusion Protein of IgG Fc and Mouse-Derived Antigen on the Surface of Pseudorabies Virus Particles Does Not Accelerate Production of Harmful Auto-Reactive Antibodies

Abstract

ABSTRACT. Previously we reported that immunization with pseudorabies virus (PRV), harboring chimeric Fc on the surface of the virus particles (PRV/Fc), induced higher immune responses than normal PRV particles. The chimeric Fc was fused with mouse transferrin receptor of transmembrane domain (mTR) and the Fc region of immunoglobulin G1. Since it has been reported that some chimeric protein of Fc and self-antigen induce auto-reactive antibodies, in this present study, we examined whether PRV/Fc induces auto-reactive antibodies that react with mTR. PRV/Fc immunized mice produced higher levels of anti-PRV antibodies and antibodies that reacted with mouse-derived 3T3/A31 cells (A31 cell), compared to normal PRV immunized mice. However, antibodies that reacted with mTR in A31 cells were not detected in both Western blot analyses and indirect immunofluorescence assay. The antibodies reacted with an antigen of approximately 16 kDa in A31 cells, but this antigen has a different molecular mass from that of mTR. The antibody also reacted with the antigen of approximately 16 kDa in RK13 cells in which the virus had been propagated. In addition, antibodies induced by immunization with normal PRV also reacted with the same antigen in A31 and RK13 cells. Moreover, neither kidney disorders, in which high levels of mTR were expressed, nor clinical symptoms of autoimmune diseases were observed in mice immunized with either PRV or PRV/Fc. These results indicated that the antibodies were not induced by mTR-Fc, but were instead induced by trace amounts of RK13 derived antigens contained in PRV or PRV/Fc preparations, and cross-reacted with equivalent molecules in mouse derived A31 cells. Therefore, this study confirmed that immunization with PRV/Fc did not induce harmful auto-reactive antibodies. KEY WORDS: chimeric IgG1 Fc, Fc, PRV.

A Vaccine Targeted at CETP Alleviates High Fat and High Cholesterol Diet-Induced Atherosclerosis and Non-Alcoholic Steatohepatitis in Rabbit

“…Since CETP is a self-antigen with low immunogenicity, which may lead to a low immune response [15] , we thus designed a novel anti-CETP vaccine (Fc-CETP 6 ) composed of the Fc domain of rabbit IgG fused to a linear repeats epitope within a region responsible for CETP-VLDL/LDL binding. The Fc domain binds to the Fc receptor, facilitating antigen delivery to antigen-presenting cells through receptor-mediated endocytosis [16] , [17] , which is more efficient than phagocytosis, leading to antigen presentation through the MHC II pathway [18] . It has been demonstrated that carrier proteins bearing linear repeats of epitope are highly effective in inducing strong B cell activation [19] .…”

A novel synthetic bipartite carrier protein for developing glycotope-based vaccines

“…It has been demonstrated that carrier proteins containing the immunoglobulin (Ig) Fc domain (IFD) facilitate uptake through receptor-mediated endocytosis [13, 18–21] and hence antigen presentation through the MHC II pathway in APCs [22–24]. It has also been demonstrated that carrier proteins containing antigen clustering domain (ACD) are highly effective in inducing strong B cell activation [12, 25–27].…”