Virus recovery by tangential flow filtration: A model to guide the design of a sample concentration process.

A simple model is developed to describe the instantaneous (rv ) and cumulative (Rv ) recovery of viruses from water during sample concentration by tangential flow filtration in the regime of constant water recovery, r. A figure of merit, M = rv r, is proposed as an aggregate performance metric that captures both the efficiency of virus recovery and the speed of sample concentration. We derive an expression for virus concentration in the sample as a function of filtration time with the rate-normalized virus loss, η=1-rvr , as a parameter. A practically relevant case is considered when the rate of virus loss is proportional to the permeation-driven mass flux of viruses to the membrane: dmaddt∼QpCf≫QpCp . In this scenario, the instantaneous recovery is constant, the cumulative recovery is decreasing as a power function of time, Rv=1-QpV0tη , η mediates the trade-off between r and rv , and M is maximized at r=ropt=12η . The proposed model can guide the design of the sample concentration process and serve as a framework for quantification and interlaboratory comparison of experimental data on virus recovery.

Application of Campylobacter jejuni Phages: Challenges and Perspectives.

Bacteriophages (phages) are the most abundant and diverse biological entities in the biosphere. Due to the rise of multi-drug resistant bacterial strains during the past decade, phages are currently experiencing a renewed interest. Bacteriophages and their derivatives are being actively researched for their potential in the medical and biotechnology fields. Phage applications targeting pathogenic food-borne bacteria are currently being utilized for decontamination and therapy of live farm animals and as a biocontrol measure at the post-harvest level. For this indication, the United States Food and Drug Administration (FDA) has approved several phage products targeting Listeria sp., Salmonella sp. and Escherichia coli. Phage-based applications against Campylobacter jejuni could potentially be used in ways similar to those against Salmonella sp. and Listeria sp.; however, only very few Campylobacter phage products have been approved anywhere to date. The research on Campylobacter phages conducted thus far indicates that highly diverse subpopulations of C. jejuni as well as phage isolation and enrichment procedures influence the specificity and efficacy of Campylobacter phages. This review paper emphasizes conclusions from previous findings instrumental in facilitating isolation of Campylobacter phages and improving specificity and efficacy of the isolates.

Human anti-α3(IV)NC1 antibody drug conjugates target glomeruli to resolve nephritis.

Current therapies to limit kidney disease progression lack specificity and often have systemic toxicity. To approach this problem, we postulated that a human monoclonal antibody (F1.1), directed against the noncollagenous-1 domain (NC1) of α3(IV) collagen that localizes in glomeruli, could serve as a vehicle for targeted drug delivery. Given enhanced exposure of the NC1 domain of α3(IV) during glomerular diseases, with limited epitope expression in other organs, α3(IV)NC1 provides an ideal target for delivery of disease-modifying agents. As a potential disease-modifying agent, we initially took advantage of recent observations that PGE2 promoted recovery after established injury during the course of nephrotoxic nephritis. To address the general applicability of the approach, the efficacy of glomerular delivery of dexamethasone was also examined. To achieve glomerular targeted therapy, PGE2 and dexamethasone were coupled to F1.1. After confirmation of the composition and activity of the conjugates, both glomerular localization and the capacity of the conjugates to modify disease were evaluated. After injection into mice with established nephritis, resolution of disease was enhanced with both agents, with normalization of histology and improved blood urea nitrogen levels in conjugate-treated mice compared with untreated mice. The results provide a novel means of targeting glomeruli during nephritis, irrespective of cause, by providing efficient drug delivery, with the potential of limiting systemic effects.