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Despite diligent vaccination efforts, influenza virus infection remains a major cause for respiratory-related illness across the globe. The less-than-optimal immunity conferred by the currently prescribed seasonal vaccines and protracted production times warrant the development of novel vaccines. Induction of an epitope-focused antibody response targeting known neutralization epitopes is a viable strategy to enhance the breadth of protection against rapidly evolving infectious viruses. We report the development of a design framework to mimic the hemagglutinin (HA) head fragment of H1-subtype viruses by delineating the interaction network of invariant residues lining the receptor binding site (RBS); a site targeted by cross-reactive neutralizing antibodies. The incorporation of multiple sequence alignment information in our algorithm to fix the construct termini and engineer rational mutations facilitates the facile extension of the design to heterologous (subtype-specific) influenza strains. We evaluated our design protocol by generating head fragments from divergent influenza A H1N1 A/Puerto Rico/8/34 and pH1N1 A/California/07/2009 strains that share a sequence identity of only 74.4% within the HA1 subunit. The designed immunogens exhibited characteristics of a well-ordered protein, and bound conformation-specific RBS targeting antibodies with high affinity, a desirable feature for putative vaccine candidates. Additionally, the bacterial expression of these immunogens provides a low-cost, rapidly scalable alternative. [ABSTRACT FROM AUTHOR]

Presents abstracts of studies on protein modifications and interactions, presented at the Experimental Biology/International Union of Physiological Sciences 2005 congress held in San Diego, California. "Phosphoserine/Threonine-Binding Domains As Dynamic Modulators of Kinase-Dependent Protein-Protein Interactions," by Duaa Mohammad, Christina Carrigan et al.; "Regulation of Receptor Endocytosis by Monoubiquitin Signals," by Linda Hicke, Joshua Schnell et al.; "The Spindle Assembly Checkpoint Is Based on the Template-Assisted Conversion of the Mad2 Protein," by Andrea Musacchio.

Presents abstracts of studies on enzyme function presented at the Experimental Biology/International Union of Physiological Sciences 2005 Congress in San Diego, California. "Computational Approaches to Empirical Protein Engineering," by Jeremy Minshull; "Directed Evolution of RuBisCo Through Genetic Selections of Metabolically Engineered Escherichia coli," by Ichiro Matsumura, et al.

We report here our retrospective observations on the use of recombinant human hyaluronidase (rHuPH20) for the facilitation of subcutaneous hydration and drug infusion. Thirty-two patients were treated with rHuPH20 in a hospice setting over a 6-month period. Of these, 26 received this agent to enhance hypodermoclysis with standard hydration fluids for symptom control of delirium, myoclonus and mild to moderate dehydration. Flow rates up to 500 mL/hr were attained without difficulty. Electrolyte replacement in hydration fluid was achieved without incident in 5 patients receiving potassium and in 1 patient receiving both potassium and magnesium. In addition to use for hydration, 6 patients received recombinant human hyaluronidase to enhance subcutaneous infusion of 9 medications, primarily because the medication dosage required subcutaneous flow rates greater than the standard 3 mL/hr. There were no significant adverse events. Induration at the infusion site occurred in 1 patient receiving hydration and higher than expected serum lidocaine concentration was observed in another patient. Based on our positive initial experience with recombinant human hyaluronidase, there is interest in expanding its use in our facility in both the inpatient and outpatient settings.