Third generation vaccine for world eradication of poliomyelitis

Great efforts have been undertaken by the World Health Organization to achieve eradication of poliomyelitis, a paralytic disease. At present, two different vaccines are available: inactivated polio vaccine (IPV) developed by Salk based on chemical inactivation of the virus and oral polio vaccine (OPV) developed by Sabin based on live attenuated virus strains. The risks associated with IPV concern the safety of the production process as it is based on highly virulent wild type strains, and in contrast, the OPV risks are associated with the reversibility of the attenuated viruses to a transmissible paralytic form. There is therefore a need for a new generation polio vaccines capable to overcome outbreaks and manufacturing risks. With the evolution of molecular virology of Sabin vaccine strains, it is now possible to design extremely genetically stable and hyperattenuated strains without the associated reversion risks. Sabin poliovirus strains were therefore genetically modified giving rise to the third generation of polio vaccine strains [1, 2]. In the present work we have explored the possibility of using the already well-established IPV production process, developed at our site [3] and integrated worldwide [4] for the production and manufacturing of third generation of IPV strains. Specifically, we have produced third generation vaccines in animal component free medium and at 50-L pilot scale. The product obtained did show acceptable yields and was immunogenic in rats. Together, our results indicate that the third generation vaccine strains produced under the flexible platform process are potential candidates which provide increased biosafety during manufacturing which is necessary after polio eradication. In addition, the flexibility and scalability of the process constitute a platform for the production of a large range of vaccines worldwide. 1. Knowlson, S., et al., New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication. PLoS Pathog, 2015. 11(12): p. e1005316. 2. Macadam, A.J., et al., Rational design of genetically stable, live-attenuated poliovirus vaccines of all three serotypes: relevance to poliomyelitis eradication. J Virol, 2006. 80(17): p. 8653-63. 3. Thomassen, Y.E., et al., Scale-down of the inactivated polio vaccine production process. Biotechnol Bioeng, 2013. 110(5): p. 1354-65. 4. Wezel, v., Monolayer growth systems: Homogeneous unit processes. Spier, R. E. and Griffiths, J. B., eds., 1985: p. 266-281

Fusarium roseum and Aspergillus oryzae-mediated enantioselective reduction of benzils to benzoins

Aspergillus oryzae OUT5048 and Fusarium roseum OUT4019 were found to be effective biocatalysts in the reduction of benzils to optically active benzoins. Easily available symmetrical benzil derivatives were reduced to the corresponding benzoins [(S)-2-hydroxy-1,2-diphenylethanones] by A. oryzae OUT5048 with tip to 94% ee and by F roseum OUT4019 with up to 98% ee, respectively. In this Work. first general method for whole-cell-mediated selective reduction of benzils to benzoins is reported. It is also shown that this method is applicable for benzils with both electron-withdrawing and electron-donating groups

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease