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Background: Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper.Methods: An enzyme-linked immunosorbent assay (ELISA) targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection.Results: In the ELISA, the anti-EBOV IVIG was shown to have a 7-fold increase in immunoglobulin G (IgG) titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately 5- to 6-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or 2 days after infection.Conclusions: These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and postexposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses. [ABSTRACT FROM AUTHOR]

Several factors, such as age and nutritional status, can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects and replicates in respiratory epithelial cells, which are also a major targets for inhaled DE. Using in vitro models of human respiratory epithelial cells, we determined the effects of an aqueous-trapped solution of DE (DEas) on influenza infections. Differentiated human nasal and bronchial epithelial cells, as well as A549 cells, were exposed to DEas and infected with influenza A/Bangkok/1/79. DEas enhanced the susceptibility to influenza virus infection in all cell models and increased the number of influenza-infected cells within 24 h post-infection. This was not caused by suppressing antiviral mediator production, since interferon (IFN) β levels, IFN-dependent signaling, and IFN-stimulated gene expression were also enhanced by exposure to DEas. Many of the adverse effects induced by DE exposure are mediated by oxidative stress. Exposure to DEas used in these studies generated oxidative stress in respiratory epithelial cells, and addition of the antioxidant glutathione-ethylester (GSH-ET) reversed the effects of DEas on influenza infections. Furthermore, DEas increased influenza virus attachment to respiratory epithelial cells within 2 h post-infection. Taken together, the results presented here suggest that in human respiratory epithelial cells oxidative stress generated by DEas increases the susceptibility to influenza infection and that exposure to DEas increases the ability of the virus to attach to and enter respiratory epithelial cells. [ABSTRACT FROM AUTHOR]