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Translational Animal Science 2024Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different...
Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. In this study, we evaluated the effect of a novel subunit targeted vaccine against bovine viral diarrhea virus (BVDV) in feedlot cattle, a major viral agent of BRD. The core of this novel vaccine is the fusion of the BVDV structural glycoprotein, E2, to a single-chain antibody, APCH, together termed, APCH-E2. The APCH antibody targets the E2 antigen to the major histocompatibility type II molecule (MHC-II) present in antigen-presenting cells. To evaluate the vaccine, 2,992 animals were randomly allocated into two groups, control group ( = 1,491) and treatment group ( = 1,501). Animals of both groups received the routine sanitary plan: two doses of clostridial, respiratory, and rabies vaccines. Animals within the treatment group also received two doses of a targeted subunit vaccine against BVDV. Serum samples were taken on the day of the first inoculation (T0) and 90 d later (T90). Viral circulation was monitored using an anti-P80 ELISA (virus-specific) and immune response was evaluated by anti-E2 ELISA (detects virus and vaccine immune responses). Only animals treated for respiratory disease were considered positive cases of BRD. Results demonstrate that the control group had significantly more animals treated for BRD cases compared to the treatment group (5.9% vs. 3.7%, = 0.02). The control group had a greater number of animals positive for anti-P80 antibodies and significantly fewer animals positive for anti-E2 antibodies compared to the treatment group (69% vs. 61% and 71% vs. 99%, respectively, = 0.003), consistent with natural viral circulation within this group. The treatment group, conversely, had fewer animals positive for anti-P80 antibodies and a greater number of animals positive for anti-E2 antibodies, consistent with a robust vaccine-induced antibody response and a reduction of the BVDV circulation within this group. The data indicate the new subunit targeted vaccine induced greater anti-E2 antibodies and reduced the amount of BVD virus circulation within the treatment group leading to a fewer number of animals needing to be treated for BRD.
PubMed: 38665216
DOI: 10.1093/tas/txae046 -
Journal of Veterinary Diagnostic... Jul 2024Rabies virus (RABV; ) is a neurotropic virus that can be transmitted to mammals by the hematophagous bat . An accurate, accessible method for the detection of RABV in... (Comparative Study)
Comparative Study
Comparison of 4 laboratory tests for the detection of bovine rabies viral infection in Paraguay: fluorescent antibody test, rapid detection test, histologic lesions, and RT-PCR.
Rabies virus (RABV; ) is a neurotropic virus that can be transmitted to mammals by the hematophagous bat . An accurate, accessible method for the detection of RABV in cattle is necessary in Paraguay; thus, we evaluated the detection of RABV using 4 techniques: fluorescent antibody test (FAT), immunochromatography rapid detection test (RDT; Anigen Rapid Rabies Ag test kit; Bionote), a reverse-transcription PCR (RT-PCR) assay, and histologic lesions in different portions of the CNS of 49 Paraguayan cattle to determine the most sensitive and specific technique. By FAT and RDT, 15 of 49 (31%) samples were positive. By RT-PCR amplification of and genes, 13 of 49 (27%) and 12 of 49 (25%) were positive, respectively. RDT had high agreement with FAT (kappa = 1); sensitivity was 100% (95% CI: 97-100%) and specificity was 100% (95% CI: 99-100%). The amplification of the and genes resulted in substantial agreement (kappa of 0.9 and 0.8, respectively) compared with FAT, and the sensitivity and specificity of the gene were 87% (95% CI: 66-100%) and 100% (95% CI: 98-100%), respectively, and those of the gene were 80% (95% CI: 56-100%) and 100% (95% CI: 98-100%), respectively. Histologic lesions observed were lymphoplasmacytic meningoencephalitis, gliosis, and neuronophagia. The agreement observed between the FAT and RDT tests suggests that RDT is an accurate tool for the detection of RABV. Histopathology can be used to confirm lesions caused by RABV and to rule out other conditions; the RT-PCR assay is useful for molecular epidemiology studies.
Topics: Animals; Rabies; Cattle; Paraguay; Rabies virus; Cattle Diseases; Sensitivity and Specificity; Reverse Transcriptase Polymerase Chain Reaction; Fluorescent Antibody Technique
PubMed: 38653733
DOI: 10.1177/10406387241246712 -
Biochemistry. Biokhimiia Mar 2024Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method...
Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method of preventing rabies disease in both animals and humans. In this study, the ability of an adjuvant based on recombinant Salmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats "Rabikan" (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the most widely used and internationally recommended method for testing effectiveness of the inactivated rabies vaccines. The value of specific activity of the tested rabies vaccine when co-administered with the adjuvant was significantly higher (48.69 IU/ml) than that of the vaccine without the adjuvant (3.75 IU/ml). Thus, recombinant flagellin could be considered as an effective adjuvant in the composition of future vaccine preparations against rabies virus.
Topics: Rabies Vaccines; Animals; Flagellin; Adjuvants, Immunologic; Mice; Rabies; Vaccines, Inactivated; Dogs; Rabies virus; Salmonella typhimurium; Female; Cats
PubMed: 38648774
DOI: 10.1134/S0006297924030155 -
Future Microbiology Apr 2024The emergence of highly zoonotic viral infections has propelled bat research forward. The viral outbreaks including Hendra virus, Nipah virus, Marburg virus, Ebola... (Review)
Review
The emergence of highly zoonotic viral infections has propelled bat research forward. The viral outbreaks including Hendra virus, Nipah virus, Marburg virus, Ebola virus, Rabies virus, Middle East respiratory syndrome coronavirus, SARS-CoV and the latest SARS-CoV-2 have been epidemiologically linked to various bat species. Bats possess unique immunological characteristics that allow them to serve as a potential viral reservoir. Bats are also known to protect themselves against viruses and maintain their immunity. Therefore, there is a need for in-depth understanding into bat-virus biology to unravel the major factors contributing to the coexistence and spread of viruses.
PubMed: 38648093
DOI: 10.2217/fmb-2023-0233 -
Radiology Case Reports Jul 2024Rabies is an acute fatal disease of the central nervous system. Neuroimaging plays an important role, especially in establishing an early diagnosis and distinguishing it...
Rabies is an acute fatal disease of the central nervous system. Neuroimaging plays an important role, especially in establishing an early diagnosis and distinguishing it from other types of encephalitis. This case report aims to give a brief review of this condition and report the less common MRI findings of the disease. We herein report a case of a 61-year-old male bitten by a stray dog who presented with fever, vomiting, headache, sialorrhea, dysarthria, dysphagia, and upper limb weakness which progressed to lower limbs on the next day. T2W and FLAIR images demonstrated subtle bilateral hyperintense signal in the deep gray matter with more apparent increased signal intensity in the white matter of the frontal and parietal lobes which shows mild diffusion restriction but no postcontrast enhancement. The diagnosis of rabies encephalitis was made based on a typical history of exposure, a compatible clinical presentation, and MRI findings. Rabies diagnosis is essentially clinical. It is definitively confirmed by the isolation of the virus from biological samples such as saliva, CSF, hair, or detection of rabies antigens or antibodies. Magnetic resonance imaging (MRI) brain used as one of the modalities of investigation for distinguishing it from other encephalitis. Rabies per se does not have any characteristic features on the MRI brain.
PubMed: 38645944
DOI: 10.1016/j.radcr.2024.03.072 -
PLoS Neglected Tropical Diseases Apr 2024Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor...
Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV). Fluorescent antibody virus neutralization test (FAVNT) was implemented to determine the neutralizing antibody titer against rabies and an individual titer ≥0·5 IU/mL indicated protection. Bayesian modeling was used to evaluate the individual duration of protection against rabies and the efficacy of two different vaccination strategies. Overall, 61% of dogs had a protective immunity one year after PV. In dogs receiving a BV, this protective immunity remained for up to one year after the BV in 95% of dogs. According to the best Bayesian model, a PV conferred a protective immunity in 82% of dogs (95% CI: 75-91%) for a mean duration of 4.7 years, and BV induced a lifelong protective immunity. Annual PV of dogs less than one year old and systematic BV solely of dogs vaccinated the year before would allow to achieve the 70% World Health Organization recommended threshold to control rabies circulation in a dog population in three to five years of implementation depending on dog population dynamics. This vaccination strategy would save up to about a third of vaccine doses, reducing cost and time efforts of mass dog vaccination campaigns. These results can contribute to optimize rabies control measures in Cambodia moving towards the global goal of ending human death from dog-mediated rabies by 2030.
Topics: Dogs; Animals; Rabies; Cambodia; Rabies Vaccines; Dog Diseases; Bayes Theorem; Antibodies, Viral; Vaccination; Male; Female; Antibodies, Neutralizing; Rabies virus
PubMed: 38635851
DOI: 10.1371/journal.pntd.0012089 -
ENeuro Apr 2024Proprioception, the sense of limb and body position, is required to produce accurate and precise movements. Proprioceptive sensory neurons transmit muscle length and...
Proprioception, the sense of limb and body position, is required to produce accurate and precise movements. Proprioceptive sensory neurons transmit muscle length and tension information to the spinal cord. The function of excitatory neurons in the intermediate spinal cord, which receive this proprioceptive information, remains poorly understood. Using genetic labeling strategies and patch-clamp techniques in acute spinal cord preparations in mice, we set out to uncover how two sets of spinal neurons, Clarke's column (CC) and -lineage neurons, respond to electrical activity and how their inputs are organized. Both sets of neurons are located in close proximity in laminae V-VII of the thoracolumbar spinal cord and have been described to receive proprioceptive signals. We find that a majority of CC neurons have a tonic-firing type and express a distinctive hyperpolarization-activated current (I). -lineage neurons, which cluster into two spatially distinct populations, are mostly a fading-firing type and display similar electrophysiological properties to each other, possibly due to their common developmental lineage. Finally, we find that CC neurons respond to stimulation of lumbar dorsal roots, consistent with prior knowledge that CC neurons receive hindlimb proprioceptive information. In contrast, using a combination of electrical stimulation, optogenetic stimulation, and transsynaptic rabies virus tracing, we find that -lineage neurons receive heterogeneous, predominantly local thoracic inputs that include parvalbumin-lineage sensory afferents and local interneuron presynaptic inputs. Altogether, we find that CC and -lineage neurons have distinct membrane properties and sensory input organization, representing different subcircuit modes of proprioceptive information processing.
Topics: Animals; Proprioception; Spinal Cord; Basic Helix-Loop-Helix Transcription Factors; Mice, Transgenic; Mice; Male; Female; Action Potentials; Sensory Receptor Cells; Patch-Clamp Techniques; Mice, Inbred C57BL; Thoracic Vertebrae
PubMed: 38627062
DOI: 10.1523/ENEURO.0331-23.2024 -
Heliyon Apr 2024Glioma is the leading cancer of the central nervous system (CNS). The efficacy of glioma treatment is significantly hindered by the presence of the blood-brain barrier...
Biomimetic nanocarriers loaded with temozolomide by cloaking brain-targeting peptides for targeting drug delivery system to promote anticancer effects in glioblastoma cells.
Glioma is the leading cancer of the central nervous system (CNS). The efficacy of glioma treatment is significantly hindered by the presence of the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB), which prevent most drugs from entering the brain and tumours. Hence, we established a novel drug delivery nanosystem of brain tumour-targeting that could self-assemble the method using an amphiphilic Zein protein isolated from corn. Zein's amphiphilicity prompted it to self-assembled into NPs, efficiently containing TMZ. This allowed us to investigate temozolomide (TMZ) for glioblastoma (GBM) treatment. To construct TMZ-encapsulated NPs (TMZ@RVG-Zein NPs), the NPs' Zein was clocked to rabies virus glycoprotein 29 (RVG29). To verify that the NPs could penetrate the BBB and precisely target and kill the GBM cancer cell line, in vitro studies were performed. The process of NPs penetrating cancer cell membranes was investigated using enzyme-linked immunosorbent assays (ELISAs) to measure the expressions of nicotinic acetylcholine receptors (nAChRs) on the U87 cell line. Therefore, effective targeted brain cancer treatment is possible by forming NP clocks, a cell-penetrating natural Zein protein with an RVG29. These NPs can penetrate the blood-brain barrier (BBB) and enter the glioblastoma (U87) cell line to release TMZ. These NPs have a distinct cocktail of biocompatibility and brain-targeting abilities, making them ideal for involving brain diseases.
PubMed: 38596030
DOI: 10.1016/j.heliyon.2024.e28256 -
Journal of Virus Eradication Mar 2024This study is a single-arm, single-center phase IV clinical trial on a rabies vaccine that has been marketed in China. The Vero cells and CTN-1V strain are used in the...
This study is a single-arm, single-center phase IV clinical trial on a rabies vaccine that has been marketed in China. The Vero cells and CTN-1V strain are used in the rabies vaccine product. The purpose of this study was to investigate the safety, immunogenicity and immune persistence of this product. One hundred and forty-nine participants were enrolled to the study, all of whom were included in the safety analysis set (SS), among which 116 participants were included in the protocol analysis set (PPS), One hundred and fifteen participants were included in the 6-month immune persistence analysis set (IPS6) and 111 in the 12-month immune persistence analysis set IPS12. Results showed that: 1) In the SS analysis set, adverse reactions were mainly pyrexia and pain at the vaccination site, the severity of which were mostly grade 1, and concentrated in 0-3 days after vaccination. No grade 3 or above adverse events and serious adverse events (SAE) related to the experimental vaccine were observed. 2) In the PPS analysis set, the antibody positive conversion rate reached 100% at 14 days after full immunization of the pre-immunized negative population; The antibody geometric mean titer (GMT) (95% CI) was 14.82 (13.00, 16.90). 3) The positive rate of serum neutralizing antibody was 93.91 % and the GMT at 1.58 IU/ml at 6 months after full immunization. The positive rate of neutralizing antibody was 85.59 % and GMT at 1.30 IU/ml at 12 months after immunization. Our results show that the human rabies vaccine with the CTN-1V strain and Vero cells as matrix had good safety, immunogenicity and immune persistence in our study.
PubMed: 38590730
DOI: 10.1016/j.jve.2024.100365 -
Biomedical and Environmental Sciences :... Feb 2024This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly...
OBJECTIVE
This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection.
METHODS
Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization.
RESULTS
A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( > 0.05).
CONCLUSION
The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.
Topics: Animals; Mice; Rabies; Antibodies, Neutralizing; Rabies Vaccines; Antibodies, Viral; Vaccination; Rabies virus; China; Post-Exposure Prophylaxis
PubMed: 38582980
DOI: 10.3967/bes2024.018