Graphical abstract

We describe a form of the autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep, linked to the repetitive inoculation of aluminum-containing adjuvants through vaccination. The syndrome shows an acute phase that affects less than 0.5% of animals in a given herd, it appears 2-6 days after an adjuvant-containing inoculation and it is characterized by an acute neurological episode with low response to external stimuli and acute meningoencephalitis, most animals apparently recovering afterward. The chronic phase is seen in a higher proportion of flocks, it can follow the acute phase, and it is triggered by external stimuli, mostly low temperatures. The chronic phase begins with an excitatory phase, followed by weakness, extreme cachexia, tetraplegia and death. Gross lesions are related to a cachectic process with muscular atrophy, and microscopic lesions are mostly linked to a neurodegenerative process in both dorsal and ventral column of the gray matter of the spinal cord. Experimental reproduction of ovine ASIA in a small group of repeatedly vaccinated animals was successful. Detection of Al(III) in tissues indicated the presence of aluminum in the nervous tissue of experimental animals. The present report is the first description of a new sheep syndrome (ovine ASIA syndrome) linked to multiple, repetitive vaccination and that can have devastating consequences as it happened after the compulsory vaccination against bluetongue in 2008. The ovine ASIA syndrome can be used as a model of other similar diseases affecting both human and animals. A major research effort is needed in order to understand its complex pathogenesis.

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The use of vaccines including aluminum (Al)-based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injectionsite granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P < .001) in the lymph nodes of the vaccine group (82.65 mg/g) compared with both adjuvant-only (2.53 mg/g) and control groups (0.96 mg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.

The major challenges in diagnosing small ruminant lentivirus (SRLV) infection include early detection and genotyping of strains of epidemiological interest. A longitudinal study was carried out in Rasa Aragonesa sheep experimentally infected with viral strains of genotypes A or B from Spanish neurological and arthritic SRLV outbreaks, respectively. Sera were tested with two commercial ELISAs, three based on specific peptides and a novel combined peptide ELISA. Three different PCR assays were used to further assess infection status. The kinetics of anti-viral antibody responses were variable, with early diagnosis dependent on the type of ELISA used. Peptide epitopes of SRLV genotypes A and B combined in the same ELISA well enhanced the overall detection rate, whereas single peptides were useful for genotyping the infecting strain (A vs. B). The results of the study suggest that a combined peptide ELISA can be used for serological diagnosis of SRLV infection, with single peptide ELISAs useful for subsequent serotyping.

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Mesenchymal stem cells can be usedin vivoas carriers of photothermal nanoparticles thanks to their ability to migrate and incorporate into tumors. A superior ablative effect is reached when using this strategy compared to the EPR effect.

Infection of orthopedic devices is a major complication in the postsurgical period generating important health issues and economic consequences. Prevention strategies could be based on local release of antibiotics from the orthopedic device itself to avoid adhesion and growth of bacteria. The purpose of this work is to demonstrate the efficiency to prevent these infections by a cefazolin-eluting, perforated stainless steel implant in an in vivo ovine model. The device was placed in the tibia of sheep, one group receiving cefazolin-loaded implants whereas the control group received empty implants. All implants were experimentally infected by direct inoculation of Staphylococcus aureus ATCC 6538. In vitro cytotoxicological studies were also performed to check the effect of antibiotic on cell viability, integrity, and cycle. Results showed that sheep receiving cefazolin-loaded devices were able to avoid implant-associated infections, with normal tissue healing process. The antibiotic release followed a local concentric pattern as demonstrated by high-performance liquid chromatography detection in tissues. The in vitro results indicate the lack of relevant cytotoxic effects for the maximum antibiotic concentration released by the device. These results demonstrate the efficiency and safety of cefazolin-eluting implants in an ovine model to prevent early postsurgical infections of orthopedic devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1976-1986, 2018.