African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

The incidence and grade of ARs during infusion of cryopreserved HPC-A are related to the amount of granulocytes in the graft.

Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes.

In connection with a project aimed at preparing new series of diketotetrazoles (see compound 1 in Scheme 1, for which two representative tautomers are shown) and pharmacophorrelated quinolinocarbonyltetrazoles, as further candidates for HIV-1 integrase inhibitors, [1] we sought a rapid entry into the synthesis of tetrazole esters 2 and/or 5-acetyltetrazoles 3 (Scheme 1). Formation of tetrazole rings by cycloaddition between nitriles and organic azides is in principle the most direct method, [2] but it usually requires very harsh conditions. Moreover, since N-unsubstituted tetrazole rings are wellrecognized bioisosters of the carboxyl groups, [2a] the development of any safe approach to tetrazoles of type 2 and 3, as well as to derivatives of general formula 4 (Scheme 1), would be of great use in the pharmaceutical industry.Most recent studies on the subject rely on a classical paper in which benzyl azide derivatives and alkyl cyanoformates (ROCO-CN) were heated without solvent at 130 8C in a sealed tube;[3] tetrazoles of type 2 can be achieved in roughly 60-70 % yields, at best. To reduce the hazards inherent to heating these polynitrogenated starting materials and products, Demko and Sharpless investigated a "click chemistry" approach [4,5] by using mainly acyl cyanides (RCO-CN) and organic azides, which allowed them to obtain compounds of type 3 (1,5-disubstituted) under solvent-free conditions, without catalysts, at 120 8C.[4a] From the more reactive p-toluenesulfonyl cyanide, excellent yields of 1,5-disubstituted tetrazoles were similarly obtained at 80-100 8C.[4b]These outstanding results encouraged us to investigate a series of potential catalysts for these [3+2]-cycloaddition reactions, aimed at achieving even safer conditions. The copper(I) complexes Cu 2 (OTf) 2 ·tol and Cu 2 (OTf) 2 ·C 6 H 6 (OTf = O 3 SCF 3 , tol = toluene) allow one to carry out most of the above reactions at room temperature, with or without solvent. This catalytic activity was not observed for other Cu I