Safety of PRRSV-2 MLV vaccines administrated via the intramuscular or intradermal route and evaluation of PRRSV transmission upon needle-free and needle delivery

Two distinct experiments (Exp) were conducted to evaluate the shedding and efficacy of 2 modified live porcine reproductive and respiratory syndrome virus (PRRSV) type 2 vaccines (MLV) when administered intramuscularly (IM) or intradermally (ID) (Exp A), and the potential of PRRSV transmission using a needle-free device (Exp B). One-hundred fifty-four, 3-week-old castrated-male, pigs were procured from a PRRSV-free herd. In Exp A, 112 pigs were randomly allocated into 4 groups of 21 pigs including IM/Ingelvac MLV (G1), IM/Prime Pac (G2), ID/Prime Pac (G3), and non-vaccination (G4). Twenty-eight remaining pigs were served as non-vaccination, age-matched sentinel pigs. G1 was IM vaccinated once with Ingelvac PRRS MLV (Ing) (Boehringer Ingelheim, Germany). G2 and G3 were IM and ID vaccinated once with a different MLV, Prime Pac PRRS (PP) (MSD Animal Health, The Netherlands), respectively. Following vaccination, an antibody response, IFN-γ-SC, and IL-10 secretion in supernatants of stimulated PBMC were monitored. Sera, tonsils, nasal swabs, bronchoalveolar lavage, urines, and feces were collected from 3 vaccinated pigs each week to 42 days post-vaccination (DPV) and assayed for the presence of PRRSV using virus isolation and qPCR. Age-matched sentinel pigs were used to evaluate the transmission of vaccine viruses and were introduced into vaccinated groups from 0 to 42 DPV. Seroconversion was monitored. In Exp B, 42 pigs were randomly allocated into 5 groups of 3 pigs each including IM/High (T1), ID/High (T2), IM/Low (T3), ID/Low (T4), and NoChal. Twenty-seven remaining pigs were left as non-challenge, age-matched sentinel pigs. The T1 and T2, and T3 and T4 groups were intranasally challenged at approximately 26 days of age with HP-PRRSV-2 at high (106) and low (103 TCID50/ml) doses, respectively. At 7 days post-challenge, at the time of the highest viremia levels of HP-PRRSV-2, T1 and T2, and T3 and T4 groups were IM and ID injected with Diluvac Forte using needles and a need-less device (IDAL 3G, MSD Animal Health, The Netherlands), respectively. Same needles or needle-less devices were used to inject the same volume of Diluvac Forte into sentinel pigs. Seroconversion of sentinels was evaluated. The results demonstrated that PP vaccinated groups (G2 and G3), regardless of the route of vaccination, had ELISA response significantly lower than G1 at 7 and 14 DPV. PP-vaccinated groups (G2 and G3) had significantly higher IFN-γ-SC and lower IL-10 secretion compared to the Ing-vaccinated group (G1). The two different MLV when administered intramuscularly demonstrated the difference in virus distribution and shedding patterns. PP-vaccinated pigs had significantly shortened viremia than the Ing-vaccinated pigs. However, ID-vaccinated pigs had lower virus distribution in organs and body fluids without virus shedding to sentinel pigs. In Exp B, regardless of the challenge dose, sentinel pigs intradermally injected with the same needle-less device used to inject challenged pigs displayed no seroconversion. In contrast, sentinel pigs intramuscularly injected with the same needle used to inject challenged pigs displayed seroconversion. The results demonstrated the transmission of PRRSV by using a needle, but not by using a needle-less device. In conclusion, our results demonstrated that ID vaccination might represent an alternative to improve vaccine efficacy and safety, and may be able to reduce the shedding of vaccine viruses and reduce the iatrogenic transfer of pathogens between animals with shared needles.

Safety of PRRSV-2 Vaccines Vaccination via Intramuscularly or Intradermally Routes and Evaluation of PRRSV Transmission and the Induction of Immune Response Between Needle- Free and Conventional Needle

Two separated experiments (Exp) were conducted to evaluate the shedding and efficacy of 2 modified live porcine reproductive and respiratory syndrome virus (PRRSV) type 2 vaccines (MLV) when administered intramuscularly (IM) or intradermally (ID) (Exp A), and the potential of PRRSV transmission using a needle-free device (Exp B). 154, castrated-male, pigs were procured from a PRRSV-free herd. In Exp A, 112 pigs were randomly allocated into 4 groups of 21 pigs including IM/Ingelvac MLV (G1), IM/Prime Pac (G2), ID/Prime Pac (G3), and non-vaccination (G4). G1 was IM vaccinated once with Ingelvac PRRS MLV (Ing) (Boehringer Ingelheim, Germany). G2 and G3 were IM and ID vaccinated once with Prime Pac PRRS (PP) (MSD Animal Health, The Netherlands), respectively. Following vaccination, an antibody response, IFN-γ-SC, and IL-10 were monitored. Sera, tonsils, nasal swabs, bronchoalveolar lavage (BAL), urines, and feces were collected from 3 vaccinated pigs each week to 42 days post-vaccination (DPV) and assayed for the presence of PRRSV using virus isolation and PCR. Age-matched sentinels were introduced weekly into vaccinated groups from 0 to 42 DPV and monitored for seroconversion. In Exp B, pigs were randomly allocated into 5 groups of 3 pigs each including IM/High (T1), ID/High (T2), IM/Low (T3), ID/Low (T4), and NoChal. The T1 and T2, and T3 and T4 groups were intranasally challenged with HP-PRRSV-2 at high (106) and low (103 TCID50/ml) doses, respectively. At 7 days post-challenge (DPC), T1 and T2, and T3 and T4 groups were IM and ID injected with Diluvac Forte using needles and a needless device (IDAL 3G, MSD Animal Health, The Netherlands), respectively. Same needles or devices were used to inject the same volume of Diluvac Forte into sentinel pigs. Seroconversion of sentinels was evaluated. The results demonstrated that PP vaccinated groups (G2 and G3), regardless of the route of vaccination, had ELISA response significantly lower than G1 at 7 and 14 DPV. PP-vaccinated groups (G2 and G3) had significantly higher IFN-γ-SC and lower IL-10 compared to the Ing-vaccinated group (G1). Based on IM, 2 different MLV had different virus distribution and shedding patterns. PP-vaccinated pigs had significantly shortened viremia than the Ing-vaccinated pigs. However, ID-vaccinated pigs had lower virus distribution in organs without virus shedding to sentinel pigs. In Exp B, ID-injected sentinel pigs had no seroconversion compared to IM-injected sentinel pigs regardless of the challenge dose. In conclusion, our results demonstrated that ID vaccination might represent an alternative to improve vaccine efficacy and safety, and may be able to reduce the shedding of vaccine viruses and reduce the iatrogenic transfer of pathogens between animals with shared needles.

3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

Copper distribution in organs and tissues of albino rats under oral administration of nanocomposite of copper oxide encapsulated in a polymeric matrix of arabinogalactan

Introduction. Based on arabinogalactan, a complex of hybrid nanobiocomposites has been created, which carry a balanced amount of macro- and microelements necessary for the body. A feature of the action of nanoparticles on the body is their ability to easily penetrate all organs and tissues. The aim of the work is to study the effect of copper arabinogalactan on the content of copper in the main tissues and organs of rats. Material and methods. The content of copper in organs and tissues of rats after a 10-day intragastric administration of a solution of copper arabinogalactan in a dose of 500 μg per kg of weight was studied by the atomic absorption method. Results. A high level of copper (above 2 μg/g) was found in wool, kidneys, liver, and heart. The brain and testes contain from 1 to 2 μg/g of copper. In the tissues of the stomach, small and large intestines, thymus, pancreas, blood, eyes, spleen, lungs, and skeletal muscles - less than 1 μg/g. Conclusion. The study of the distribution of copper in the organs of rats after oral administration of the nanocomposite of copper oxide with arabinogalactan demonstrated the main target organs for the accumulation of the element to be the kidneys, liver, brain, and stomach. The different character of the accumulation of copper in the tissues of the body of the rats received arabinogalactan of copper in the form of a nanocomposite, may indicate the selective ability of tissues and organs to accumulate this element. For further work on the possible use of the drug for medicinal purposes, it is necessary to take into account the peculiarities of biodistribution and bioaccumulation in various organs.

Pharmacokinetic properties of an innovative nootropic agent based on a derivative of 3,7-diazabicyclo[3.3.1]nonane

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.

Brucella melitensis Rev.1 vaccination generates a higher shedding risk of the vaccine strain in Alpine ibex (Capra ibex) compared to the domestic goat (Capra hircus)

Epidemiological investigations implemented in wild and domestic ruminants evidenced a reservoir for Brucella in Capra ibex in the French Alps. Vaccination was considered as a possible way to control Brucella infection in this wildlife population. Twelve ibexes and twelve goats were allocated into four groups housed separately, each including six males or six non-pregnant females. Four to five animals were vaccinated and one or two animals were contact animals. Half of the animals were necropsied 45 days post-vaccination (pv), and the remaining ones at 90 days pv. Additional samples were collected 20 and 68 days pv to explore bacterial distribution in organs and humoral immunity. Neither clinical signs nor Brucella-specific lesions were observed and all vaccinated animals seroconverted. Brucella distribution and antibody profiles were highly contrasted between both species. Proportion of infected samples was significantly higher in ibex compared to goats and decreased between 45 and 90 days pv. Two male ibex presented urogenital excretion at 20 or 45 days pv. The bacterial load was higher 45 days in ibexes compared to goats, whereas it remained moderate to low 90 days pv in both species with large variability between animals. In this experiment, differences between species remained the main source of variation, with low impact of other individual factors. To conclude, multiplicative and shedding capacity of Rev.1 was much higher in ibex compared to goats within 90 days. These results provide initial information on the potential use in natura of a commercial vaccine.

In Vitro and In Vivo Testing to Determine Cd Bioaccessibility and Bioavailability in Contaminated Rice in Relation to Mouse Chow

A combination of an in vitro physiologically based extraction test (PBET) and an in vivo mouse model was used to determine Cd oral bioaccessibility and estimate bioavailability in Cd-contaminated rice. The PBET found lower Cd bioaccessibility in the intestinal stage (40–50%) than in the gastric stage (93–98%) for both rice and mouse chow. No significant difference was found in Cd bioaccessibility between contaminated rice and Cd-amended mouse chow in the gastric or gastrointestinal phase (except for rice 1). The result of the in vivo bioassay revealed that Cd absorption in the kidney or liver of mice fed with contaminated rice were significantly higher than in the mouse chow group containing an equal Cd concentration. Correlation analysis between concentrations of different elements in mouse chow or rice and Cd concentrations in mice kidney or liver showed that Fe, Ca, Cu, and Zn had significant negative correlation (r2 > 0.7, p < 0.01). These results suggest that nutritional elements in the diet could affect Cd absorption and distribution in organs and that different food matrices may result in unequal Cd health risks at an equal Cd concentration due to the specific mineral content of food.

Justification of the need for correction selenium status in the treatment of thyrotopathy among Ukrainians (review of literature and their own observations)

The review analyzes the evidence base presented in scientific publications, which proves the importance of selenium for normal functioning of the thyroid gland. Presented data have connections with the involvement of selenium in the formation of thyroid hormones, their distribution in organs and systems, and peripheral metabolism. The role of the main selenoproteins participating in these processes is specified. The data of PubMed on the availability of selenium to residents of European countries is given, which is mainly estimated as suboptimal, but in a number of countries as insufficient. The author cited the results of her own studies of the level of selenium in the hair in certain groups of female patients and thyopathology, living in different regions of Ukraine. Based on the literature review and own observations, the author focuses on the relevance of the problem of selenium deficiency in Ukraine and on the need to expand research in this direction, because today there are opportunities with selenium-containing drugs to increase the effectiveness of prevention and treatment of various thypathology.