We report the humanization and characterization of monoclonal antibody (MAb) T1-2 or tefibazumab, a monoclonal antibody that recognizes clumping factor A expressed on the surface of Staphylococcus aureus. We demonstrate that the binding kinetics of MAb T1-2 is indistinguishable compared to that of its murine parent. Furthermore, MAb T1-2 is shown to enhance the opsonophagocytic uptake of ClfA-coated latex beads, protect against an intravenous challenge in a prophylactic model of rabbit infective endocarditis, and enhance the efficacy of vancomycin therapy in a therapeutic model of established infective endocarditis.

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Background: Cardiac surgery using cardiopulmonary bypass carries a high risk of bleeding and need for blood transfusion. Blood administration is associated with increased rates of morbidity and mortality. Perioperatively, strategies are often employed to reduce blood transfusions in high-risk patients or in situations where blood transfusion is contraindicated. Normovolemic hemodilution is a blood conservation technique used during cardiac surgery that involves replacement of blood with fluids. SANGUINATE® (PEGylated carboxyhemoglobin bovine) is a novel hemoglobin-based oxygen carrier that can deliver oxygen effectively to tissues in the presence of severe hypoxia. The use of a hemoglobin-based oxygen carrier during hemodilution may augment tissue oxygen delivery and reduce blood transfusion. Methods: Six standardized cardiopulmonary bypass runs simulating normovolemic hemodilution using varying proportions of bovine whole blood and SANGUINATE were performed. Pump speed, flow rate, line pressures, hemoglobin concentration, oxygenation, and degree of anticoagulation were assessed at regular intervals. Membrane oxygenators and arterial line filters were inspected for evidence of clotting following each run. Results: Increases in the pressure drop across the membrane oxygenator were detected during runs 5 and 6. Median activated clotting time values were able to be maintained at goal during the runs, and SANGUINATE did not appear to be thrombogenic. Hemoglobin concentration decreased following the addition of SANGUINATE. Oxygenation was maintained during all runs that included SANGUINATE. Conclusion: SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass.

A familial aggregate of 7 cases of Hodgkin’s disease, 3 of common variable immunodeficiency, 8 of other lymphoreticular malignancies, and 4 of embryonic tumours is being studied in a multidiscipline fashion to search for clues to aetiology. Part of the investigation was to examine immunoglobulin concentrations in the whole population, both in family members and in other members of the same communities. Analysis of the data on some 1,200 people revealed the expected changes with age in IgG, IgA and IgM. A striking age-related pattern for IgD with a peak in puberty and young adulthood was noted. The expected sex differences were also seen which were marked for IgM and mild for IgG. The immunoglobulin concentrations in families in which there had been a case of malignancy or immunodeficiency showed two deviations from values derived from controls: (i) relatives of the common variable immunodeficiency patients showed an elevated mean IgM, and (ii) relatives of the Hodgkin’s disease patients and of the lymphosarcoma patients showed mean IgD concentrations that were 20 times as high as that of controls from outside the study population and were the highest of all the groups within it. However, when compared with the controls from elsewhere in the province, the mean IgD values in all subgroups of the study population were significantly elevated including in a genetically separate group not descended from an important founding couple. It is concluded that factors causing elevated IgD in this high lymphoma incidence population are likely to be predominantly determined by environment rather than by genetic factors. We postulate that the increase may be partly due to the low socio-economic status of the population, but the reason why the highest values are found in the lymphoma families is not immediately clear.