To establish a method for evaluation of the efficacy of a classical swine fever virus (CSFV) subunit vaccine in rabbits as determined via humoral immune responses to the virus.
40 specific pathogen–free rabbits.
Rabbits were randomly assigned to 4 groups (10 rabbits/group) for SC injection of 0.05, 0.1, and 0.2 mL of a CSFV subunit E2 vaccine (representing 1.15, 2.3, or 4.6 μg of E2 protein/dose, respectively) or saline (0.9% NaCl) solution. Blood samples were collected 21 days after vaccination for measurement of the antibody response against CSFV via ELISA and virus neutralization methods. On the same day, the CSFV Chinese (C) strain was injected into an ear vein. Vaccine efficacy was determined by monitoring of rabbits for pyrexia for 4 days and measurement of viral copies in spleen lysates at the end of the study. Reproducibility of the antibody response was tested with 2 other batches of the vaccine at the minimum immunization dose identified for the initially tested batch.
The E2 protein dose of the initially tested vaccine was positively correlated with the antibody response and protection rate in rabbits. The identified minimum immunization dose per rabbit was 0.1 mL, representing an E2 protein content of approximately 2.3 μg, and reproducibility of the antibody response to vaccination with the 2 other batches at this dose was good.
CONCLUSIONS AND CLINICAL RELEVANCE
A method was established in rabbits for evaluation of the efficacy of a CSFV subunit vaccine that could help in the optimization of later large-scale vaccine production and quality control processes as well as in the clinical application of the vaccine.
OBJECTIVE: To investigate the distribution of T-cell markers (CD4 and CD8α) in lymphoid organs of newborn, juvenile, and adult yaks.
ANIMALS: 15 healthy male yaks of various ages from highland plateaus.
PROCEDURES: Yaks were allocated to groups on the basis of age (newborn [1 to 7 days old; n = 5], juvenile [5 to 7 months old; 5], and adult [3 to 4 years old; 5]). The thymus, spleen, 5 mesenteric lymph nodes, and 5 hemal nodes were harvested from each yak within 10 minutes after euthanasia. Morphological characteristics of those lymphoid organs were assessed by histologic examination; expression of CD4 and CD8α mRNAs and proteins were measured by quantitative real-time PCR assay and immunohistochemical staining.
RESULTS: Among the lymphoid organs evaluated, expressions of CD4 and CD8α mRNAs were highest in the thymus in all age groups. In newborn lymphoid organs, CD4 mRNA expression and CD4+ cell distribution were more predominant, whereas in juvenile and adult lymphoid organs, CD8α mRNA expression and CD8α+ cell distribution were more predominant. The CD4+ and CD8α+ cells were mainly located in the cortex and medulla of the thymus, the medulla of the hemal nodes and mesenteric lymph nodes, the periarteriolar lymphoid sheaths, and the red pulp of the spleen.
CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the CD4 mRNA expression and CD4+ T-cell distribution in yak lymphoid organs decreased and CD8α mRNA expression and CD8α+ T-cell distribution increased with age. Moreover, CD8α+ cells were present in the follicles of yaks’ secondary lymphoid organs, which differs from findings for other mammals.
OBJECTIVE To evaluate age-related changes in the morphology and expression of cluster of differentiation 3 (CD3), S100 β, and caspase-3 of the thymus of healthy yaks (Bos grunniens).
ANIMALS 15 healthy male yaks of various ages from highland plateaus.
PROCEDURES Yaks were allocated to 3 groups on the basis of age (newborn [1 to 7 days old; n = 5], juvenile [5 to 7 months old, 5], and adult [3 to 4 years old; 5]) and euthanized. The thymus was harvested from each yak within 10 minutes after euthanasia. Morphological characteristics were assessed by histologic examination and transmission electron microscopy. Expression of CD3, S100 β, and caspase-3 mRNA and protein was measured by quantitative real-time PCR assay, Western blot analysis, and immunohistochemical staining.
RESULTS As age increased, functional thymic tissue was replaced with adipose and connective tissues and the thymic capsule thickened. Expression of CD3 and S100 β mRNA and protein decreased with age, whereas expression of caspase-3 mRNA and protein increased with age. Immunohistochemical staining revealed that CD3-positive thymocytes were located within both the thymic cortex and medulla, S100 β–positive thymic dendritic cells were located in the corticomedullary junction and medulla, and caspase-3–positive thymocytes were diffusely scattered throughout the cortex and medulla.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that age-related thymic changes in yaks that live on highland plateaus were similar to those observed in humans and other mammals. Thus, yaks might serve as a model to study thymic immune system adaptations to high elevations.
To compare the pharmacokinetics of cefquinome sulfate in ducklings and goslings after IV or IM administration of a single dose.
216 healthy Muscovy ducklings (Cairina moschata) and 216 healthy Sichuan white goslings (Anser cygnoides).
Ducklings and goslings were each randomly assigned to 3 groups (n = 72/group) that received a single dose (2 mg/kg) of injectable cefquinome sulfate administered IV or IM or of injectable cefquinome sulfate suspension administered IM. Blood samples were collected at various points after drug administration (n = 6 birds/time point). Plasma cefquinome concentrations were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated with a 2-compartment model method.
After IV injection, mean distribution half-life of cefquinome was longer in goslings (0.446 hours) than in ducklings (0.019 hours), whereas volume of distribution at steady state was greater (0.432 vs 0.042 L/kg) and elimination half-life was slower (1.737 vs 0.972 hours). After IM administration of injectable cefquinome sulfate, bioavailability of the drug was higher in goslings (113.9%) than in ducklings (67.5%). After IM administration of injectable cefquinome sulfate suspension, bioavailability was also higher in goslings (123.1%) than in ducklings (96.8%), whereas elimination half-life was slower (6.917 vs 1.895 hours, respectively).
CONCLUSIONS AND CLINICAL RELEVANCE
In goslings, IV administration of cefquinome resulted in slower distribution and metabolism of the drug than in ducklings and IM administration resulted in higher bioavailability. The delayed-release effect of the injectable cefquinome sulfate suspension when administered IM was observed only in goslings.
Orthohantaviruses (genus Orthohantavirus, family Hantaviridae of order Bunyavirales) are rodent-borne viruses causing 2 human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which are mainly prevalent in Eurasia and the Americas, respectively. We initiated this study to investigate and analyze the Orthohantaviruses infection in rodent reservoirs and humans in the Hubei Province of China from 1984 to 2010.
The study included 10,314 mouse and 43,753 human serum samples.
In this study, we analyzed the incidence of Orthohantavirus infection in humans and observed changes in rodent reservoirs in Hubei Province.
The results indicated that although the incidence of HFRS declined from the 1990s, the human inapparent infection did not decrease dramatically. Although elements of the disease ecology have changed over the study period, Apodemus agrarius and Rattus norvegicus remain the major species and a constituent ratio of Rattus norvegicus increased. Rodent population density fluctuated between 16.65% and 2.14%, and decreased quinquennially, showing an obvious downward trend in recent years. The average orthohantaviruses-carrying rate was 6.36%, of which the lowest rate was 2.92% from 2006 to 2010. The analysis of rodent species composition showed that Rattus norvegicus and Apodemus agrarius were the dominant species over time (68.6% [1984 to 1987] and 90.4% [2000 to 2011]), while the composition and variety of other species decreased. The density of rodents was closely related to the incidence of HFRS (r = 0.910, P = .032).
Our long-term investigation demonstrated that the occurrence of HFRS is closely related to rodent demographic patterns. Therefore, rodent monitoring and rodent control measures for prevention against HFRS in Hubei are warranted.
OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors.
ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer.
PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro. Effects of cisplatin (IV) and HA-Pt (SC) in rodents were tested by clinicopathologic assays. In the clinical trial, dogs with cancer received 1 to 4 injections of HA-Pt (10 to 30 mg/m2, intratumoral or peritumoral, q 3 wk). Blood samples were collected for pharmacokinetic analysis; CBC, serum BUN and creatinine concentration measurement, and urinalysis were conducted before and 1 week after each treatment. Some dogs underwent hepatic enzyme testing. Tumors were measured before the first treatment and 3 weeks after each treatment to assess response.
RESULTS No adverse drug effects were detected in pretrial assessments in rodents. Seven of 16 dogs completed the study; 3 had complete tumor responses, 3 had stable disease, and 1 had progressive disease. Three of 7 dogs with oral and nasal squamous cell carcinoma (SCC) that completed the study had complete responses. Myelosuppression and cardiotoxicosis were identified in 6 and 2 dogs, respectively; none had nephrotoxicosis. Four of 5 dogs with hepatic enzymes assessed had increased ALT activities, attributed to diaquated cisplatin products in the HA-Pt. Pharmacokinetic data fit a 3-compartment model.
CONCLUSIONS AND CLINICAL RELEVANCE HA-Pt treatment resulted in positive tumor responses in some dogs, primarily those with SCC. The adverse effect rate was high.
IMPACT FOR HUMAN MEDICINE Oral SCC in dogs has characteristics similar to human head and neck SCC; these results could be useful in developing human treatments.