Immunotoxicity assessment of rice-derived recombinant human serum albumin using human peripheral blood mononuclear cells.

Human serum albumin (HSA) is extensively used in clinics to treat a variety of diseases, such as hypoproteinemia, hemorrhagic shock, serious burn injuries, cirrhotic ascites and fetal erythroblastosis. To address supply shortages and high safety risks from limited human donors, we recently developed recombinant technology to produce HSA from rice endosperm. To assess the risk potential of HSA derived from Oryza sativa (OsrHSA) before a First-in-human (FIH) trial, we compared OsrHSA and plasma-derived HSA (pHSA), evaluating the potential for an immune reaction and toxicity using human peripheral blood mononuclear cells (PBMCs). The results indicated that neither OsrHSA nor pHSA stimulated T cell proliferation at 1x and 5x dosages. We also found no significant differences in the profiles of the CD4(+) and CD8(+) T cell subsets between OsrHSA- and pHSA-treated cells. Furthermore, the results showed that there were no significant differences between OsrHSA and pHSA in the production of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and IL-4. Our results demonstrated that OsrHSA has equivalent immunotoxicity to pHSA when using the PBMC model. Moreover, this ex vivo system could provide an alternative approach to predict potential risks in novel biopharmaceutical development.

Hyaluronic acid viscosupplements from avian and non-mammalian sources exhibit biocompatibility profiles with unique, source-specific, antigenic profiles.

The objective of this study was to evaluate and compare the biocompatibility profiles of hyaluronic acid (HA) viscosupplements from avian and non-mammalian sources. Inflammatory and immune reactions were assessed in models of both clinically relevant and stringent immunological exposure conditions. Experiments were conducted to evaluate tissue reactions and immunological responses and assess antibody formation with the capacity to bind directly to and cross-react with the different viscosupplements. Mice were exposed to viscosupplements using the air pouch inflammation model and specific immunization using Freund's complete adjuvant (FCA). Murine pouch membrane tissue reactions revealed generally mild to moderate responses, with cellular infiltration and cytokine profiles of pouch tissue characteristic of predominantly fibroblastic responses rather than marked inflammatory reactions. In vitro testing indicated that pouch injections did not elicit detectable T-cell proliferative responses, while antibody assays revealed that mice immunized with viscosupplements in FCA and subsequently boosted were capable of mounting an antibody response with a range of specificities. High reactivity to avian serum albumin was seen in sera from mice injected with HA from an avian source, while low positive reactivity to the bacterial antigen Staphylococcal Lipotechoic Acid was observed in sera from mice injected with HA from bacterial sources. These specificities did not indicate any propensity to cross-react, suggesting that patients with adverse immune responses to HA from an avian source should be unresponsive to subsequent injection with HA from a non-avian source. Overall, the findings demonstrate that viscosupplements exhibit good biocompatibility profiles in the murine air pouch, but when provoked to elicit immunological reactions exhibit unique antigenic spectra. These findings suggest that an immunologically mediated immune reaction directed against avian proteins should not necessarily be a contraindication for the administration of non-avian viscosupplements.

Immunomodulatory and therapeutic potential of a mycelial lectin from Aspergillus nidulans.

Lectins bind to surface receptors on target cells, and activate a cascade of events, eventually leading to altered immune status of host. The immunomodulatory potential of purified lectin from Aspergillus nidulans was evaluated in Swiss albino mice treated intraperitoneally with seven different doses of purified lectin. Lectin prevented BSA-induced Arthus reaction and systemic anaphylaxis. The enhanced functional ability of macrophages was evident from respiratory burst activity and nitric oxide production in splenocyte cultures. Interferon-gamma and interleukin-6 levels were significantly up-regulated in treated groups. Maximum stimulatory effect was observed at the dose of 1.5 mg/kg body weight. Therapeutic potential of A. nidulans lectin was assessed against trinitrobenzene sulfonic acid-induced ulcerative colitis in male Wistar rats. Rats pre-treated with 80 mg/kg body weight of purified lectin intraperitoneally prior to colitis induction showed lesser disease severity and recovery within 7 days, while rats post-treated with the same dose showed recovery in 11 days. The results demonstrate immunomodulatory effects of A. nidulans lectin in Swiss albino mice, resulting in improved immune status of the animals and unfold its curative effect against ulcerative colitis in rat model. This is the first report on immunomodulatory and therapeutic potential of a lectin from microfungi.

Adverse reactions to human serum albumin.

OBJECTIVE: To describe the adverse effects associated with human serum albumin (HSA) administration. DATA SOURCES: A MEDLINE search and bibliography scanning were used to identify pertinent review articles, clinical studies, and case reports. STUDY SELECTION: Emphasis was placed on reporting the results of human studies with the primary objective of investigating adverse effects attributable to HSA administration. Clinical trials that reported the occurrence of adverse effects possibly associated with HSA were also reviewed. Animal data were included where pertinent. DATA EXTRACTION: Although isolated case reports were reviewed, data were primarily extracted from human studies involving large series of patients or studies that were randomized and prospective in nature. DATA SYNTHESIS: Alterations in coagulation, renal, cardiovascular, and pulmonary functions were identified as potential adverse effects following the administration of HSA. Occurrences of hypersensitivity reactions, trace metal loading, and serum amino acid alterations associated with these infusions were also noted and are described here. Pulmonary and cardiovascular systems appear to be particularly prone to complications from excessive HSA administration. Adverse effects such as HSA-induced hypersensitivity reactions may be severe, but occur infrequently. CONCLUSIONS: Controlled studies involving large numbers of patients are not currently available for an accurate assessment of the incidence of adverse effects attributable to HSA administration. Many of the reported reactions appear to be extensions of albumin's pharmacologic activities and would be expected to worsen following large doses of HSA.