Dataset Information

PROPHYLACTIC ANTIBODY TREATMENT AND INTRAMUSCULAR IMMUNIZATION REDUCE INFECTIOUS HUMAN RHINOVIRUS 16 LOAD IN THE LOWER RESPIRATORY TRACT OF CHALLENGED COTTON RATS.

ABSTRACT: Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.

SUBMITTER: Blanco JC

PROVIDER: S-EPMC4199241 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PROPHYLACTIC ANTIBODY TREATMENT AND INTRAMUSCULAR IMMUNIZATION REDUCE INFECTIOUS HUMAN RHINOVIRUS 16 LOAD IN THE LOWER RESPIRATORY TRACT OF CHALLENGED COTTON RATS.

Blanco Jorge C G JC Core Susan S Pletneva Lioubov M LM March Thomas H TH Boukhvalova Marina S MS Kajon Adriana E AE

Trials in vaccinology 20140101

Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (<i>Sigmodon hispidus</i>) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host ...[more]

PMID: 25328560

Similar Datasets

Project description:BackgroundThere is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This is an update of a review first published in 2012.ObjectivesTo determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth.Search methodsWe searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2017) and reference lists of retrieved studies.Selection criteriaRandomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials.Data collection and analysisTwo review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach.Main resultsThree studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates.Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta).Authors' conclusionsVery low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.

Project description:Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To develop an intervention strategy that is non-specific yet effective against diverse Salmonella serovars, we explored the prophylactic use of a cytokine to decrease Salmonella in swine by boosting the host's innate immune system. Granulocyte-colony stimulating factor (G-CSF) is the major cytokine regulating the production, differentiation, function, and survival of neutrophils. Neutrophils play a critical role in the response to Salmonella; therefore, we evaluated the vectored-delivery of porcine G-CSF as a prophylactic to reduce Salmonella in pigs. Crossbred pigs, 5 weeks of age, were intramuscularly injected with a replication-defective human adenovirus (Ad5) engineered to express porcine G-CSF (Ad5-G-CSF, n = 9). Control pigs received the same Ad5 vector lacking the gene encoding G-CSF (Ad5-empty, n = 7). Four days later, all pigs (n = 16) were intranasally inoculated with 1 × 10(7) colony forming unit (CFU) of Salmonella enterica serovar Typhimurium UK1. At 2 and 3 days post-challenge with Salmonella, Ad5-G-CSF-treated pigs shed significantly less Salmonella (~10(3) CFU/g) in their feces than Ad5-empty-treated pigs (~10(4)-10(5) CFU/g; P < 0.05). A significant 4-log reduction in tonsil colonization was also observed in the Ad5-G-CSF-treated pigs at 7 days post-challenge (P < 0.05). In the gastrointestinal tract, the Peyer's patch region of the ileum exhibited a significant 0.5-log reduction in colonization in the Ad5-G-CSF-treated pigs (P < 0.05). The microbiota of all challenged pigs was assessed by sequencing and analyzing the V1-V3 region of the 16S rRNA gene from fecal DNA samples. The microbial community structure of Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF-treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF administration mitigated changes in the microbial community structure caused by Salmonella challenge. Collectively, these data suggest that delivery of a targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce Salmonella colonization, potentially during periods of immunological stress.

Project description:The replication of picornaviruses has been described to cause fragmentation of the Golgi apparatus that blocks the secretory pathway. The inhibition of major histocompatibility complex class I upregulation and cytokine, chemokine and interferon secretion may have important implications for host defense. Previous studies have shown that disruption of the secretory pathway can be replicated by expression of individual nonstructural proteins; however the situation with different serotypes of human rhinovirus (HRV) is unclear. The expression of 3A protein from HRV14 or HRV2 did not cause Golgi apparatus disruption or a block in secretion, whereas other studies showed that infection of cells with HRV1A did cause Golgi apparatus disruption which was replicated by the expression of 3A. HRV16 is the serotype most widely used in clinical HRV challenge studies; consequently, to address the issue of Golgi apparatus disruption for HRV16, we have systematically and quantitatively examined the effect of HRV16 on both Golgi apparatus fragmentation and protein secretion in HeLa cells. First, we expressed each individual nonstructural protein and examined their cellular localization and their disruption of endoplasmic reticulum and Golgi apparatus architecture. We quantified their effects on the secretory pathway by measuring secretion of the reporter protein Gaussia luciferase. Finally, we examined the same outcomes following infection of cells with live virus. We demonstrate that expression of HRV16 3A and 3AB and, to a lesser extent, 2B caused dispersal of the Golgi structure, and these three nonstructural proteins also inhibited protein secretion. The infection of cells with HRV16 also caused significant Golgi apparatus dispersal; however, this did not result in the inhibition of protein secretion. Importance: The ability of replicating picornaviruses to influence the function of the secretory pathway has important implications for host defense. However, there appear to be differences between different members of the family and inconsistent results when comparing infection with live virus to expression of individual nonstructural proteins. We demonstrate that individual nonstructural HRV16 proteins, when expressed in HeLa cells, can both fragment the Golgi apparatus and block secretion, whereas viral infection fragments the Golgi apparatus without blocking secretion. This has major implications for how we interpret mechanistic evidence derived from the expression of single viral proteins.

Dataset Information

PROPHYLACTIC ANTIBODY TREATMENT AND INTRAMUSCULAR IMMUNIZATION REDUCE INFECTIOUS HUMAN RHINOVIRUS 16 LOAD IN THE LOWER RESPIRATORY TRACT OF CHALLENGED COTTON RATS.

Publications

PROPHYLACTIC ANTIBODY TREATMENT AND INTRAMUSCULAR IMMUNIZATION REDUCE INFECTIOUS HUMAN RHINOVIRUS 16 LOAD IN THE LOWER RESPIRATORY TRACT OF CHALLENGED COTTON RATS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets