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Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons. Thus the development of therapeutic neuroprotection and neurorescue strategies to mitigate disease progression is important. In this study we evaluated the neuroprotective/rescue effects of erythropoietin Fc fusion protein (EPO-Fc) and carbamylated erythropoietin Fe fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. Adult female Sprague-Dawley rats received intraperitoneal injection of EPO-Fc, CEPO-Fc or PBS. Behavioral evaluations consisted of rota-rod, cylinder and amphetamine-induced rotation tests. In the neuroprotection experiment, the CEPO-Fc group demonstrated significant improvement compared with the EPO-Fc group on the amphetamine-induced rotation test throughout the four-week follow-up period. Histologically, significantly more tyrosine hydroxylase (TH)-positive neurons were recognized in the substantia nigra (SN) pars compacta in the CEPO-Fc group than in the PBS and EPO-Fc groups. In the neurorescue experiment, rats receiving CEPO-Fc showed significantly better behavioural scores than those receiving PBS. The histological data concerning striatum also showed that the CEPO-Fc group had significantly better preservation of TH-positive fibers compared to the PBS and EPO-Fc groups. Importantly, there were no increases in hematocrit or hemoglobin levels in the CEPO-Fc group in either the neuroprotection or the neurorescue experiments. In conclusion, the newly developed CEPO-Fc might confer neuroprotective and neurorescue benefits in a rat model of Parkinson's disease without the side effects associated with polycythemia. CEPO-Fc might be a therapeutic tool for patients with Parkinson's disease.

Anti-idiotypic antibodies directed against potentially neutralizing anti-HIV-1 antibodies may mimic epitopes on gp41 otherwise cryptic to the immune system. This study reports the generation of murine monoclonal antibody Ab2/3H6 blocking the binding of human Ab1 2F5 to the synthetic epitope and to gp160 in an enzyme-linked immunosorbent competition assay. Ab2/2H6 diminished the neutralizing potency of 2F5 in an in-vitro neutralization assay. Ab2/3H6 Fab fragments were capable of inducing neutralizing immune and 2F5-specific responses in B6D2F1 mice applying a simple prime-boost regimen of immunization.

Background Sexually transmitted diseases are predominantly acquired via mucosal membranes of the rectal or genital tract during sexual intercourse. This major port of virus entry is naturally defended by the humoral immune response, with immunoglobulin A (IgA) as the primary antibody class to elicit mucosal immunity. Dimeric IgA (dIgA) reaches the luminal side of mucosal tissues by transcytosis through epithelial cells lining the mucosa. In a first step, dIgAs specifically bind to the basolaterally expressed polymeric immunoglobulin receptor (pIgR) on epithelial cells. For release of IgAs on the luminal side the extracellular portion, termed secretory component (SC), remains attached to the antibody to form secretory IgA (sIgA) [1,2]. One example of a sexually transmitted disease is the human immunodeficiency virus (HIV) which annually infects several million individuals on a global scale and potentially leads to the acquired immunodeficiency syndrome (AIDS). Although current therapies can reduce disease progression in infected individuals, no cure is yet available or within reach in near future. As a consequence increased attention is now being paid to develop drugs that could prevent virus acquisition. 3D6 and 4B3 are two monoclonal antibodies (mAb) which have originally been isolated as IgG1 isotype from seroconverted HIV-1 patients and bind to the principal immunodominant domain of gp41. In the course of this project both mAbs were isotype switched to IgA1. Recombinant CHO cell lines were established for the production of 3D6 and 4B3 as dimeric as well as secretory IgA. While dIgA were expressed by a single cell line, sIgA are produced by a biochemical association of dIgA with SC. Both dIgA and sIgA variants were characterized and the contribution of the heavily glycosylated SC on IgA stability will be investigated.