-
Journal of Feline Medicine and Surgery Feb 2024Some expert groups recommend that cats should be vaccinated with non-adjuvanted feline leukaemia virus (FeLV) and rabies vector vaccines, which, in the European Union,...
OBJECTIVES
Some expert groups recommend that cats should be vaccinated with non-adjuvanted feline leukaemia virus (FeLV) and rabies vector vaccines, which, in the European Union, are currently not licensed for concurrent use and have to be administered at least 14 days apart (different from the USA) and thus at separate visits, which is associated with more stress for cats and owners. The aim of this study was to assess the anti-rabies antibody response in cats after vaccination against rabies and FeLV at concurrent vs separate (4 weeks apart) visits using two canarypox-vectored vaccines (Purevax Rabies and Purevax FeLV; Boehringer Ingelheim) and to evaluate the occurrence of vaccine-associated adverse events (VAAEs).
METHODS
Healthy FeLV antigen-negative client-owned kittens (n = 106) were prospectively included in this randomised study. All kittens received primary vaccinations against rabies (week 0) and FeLV (weeks 4 and 8). After 1 year, the study group (n = 52) received booster vaccinations against rabies and FeLV concurrently at the same visit (weeks 50-52). The control group (n = 54) received booster vaccinations against rabies (weeks 50-52) and FeLV (weeks 54-56) separately. Anti-rabies virus antibodies (anti-RAV Ab) were determined by fluorescent antibody virus neutralisation assay at weeks 4, 50-52 and 54-56, and compared between both groups using a Mann-Whitney U-test.
RESULTS
Four weeks after the first rabies vaccination, 87/106 (82.1%) kittens had a titre ⩾0.5 IU/ml and 19/106 (17.9%) had a titre <0.5 IU/ml. Four weeks after the 1-year rabies booster, all cats had adequate anti-RAV Ab according to the World Organisation for Animal Health (⩾0.5 IU/ml), and the titres of the study group (median = 14.30 IU/ml) and the control group (median = 21.39 IU/ml) did not differ significantly ( = 0.141). VAAEs were observed in 7/106 (6.6%) cats.
CONCLUSIONS AND RELEVANCE
Concurrent administration of Purevax FeLV and Purevax Rabies vector vaccines at the 1-year booster does not interfere with the development of anti-RAV Ab or cause more adverse effects and thus represents a better option than separate vaccination visits for cats and owners.
Topics: Animals; Cats; Antibodies, Viral; Cat Diseases; Immunity, Humoral; Leukemia Virus, Feline; Rabies; Vaccination; Viral Vaccines
PubMed: 38358295
DOI: 10.1177/1098612X231218643 -
Biomedicine & Pharmacotherapy =... Mar 2024Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting...
Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.
Topics: Animals; Mice; Polymers; Micelles; Carbon Dioxide; Polyethylene Glycols; Neuroblastoma; Peptides; Carbonates; Formates
PubMed: 38354570
DOI: 10.1016/j.biopha.2024.116272 -
Preventive Veterinary Medicine Apr 2024The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to...
The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency "contingency" actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017-2019 and 2018-2021) and one in Virginia (2017-2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (>0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2-3 years of each contingency action.
Topics: Animals; United States; Rabies; Raccoons; Ohio; Virginia; Animals, Wild; Administration, Oral; Rabies Vaccines
PubMed: 38354432
DOI: 10.1016/j.prevetmed.2024.106145 -
Microbiology Resource Announcements Mar 2024The complete coding sequence of a rabies lyssavirus (RABV) detected in a black bear () was generated. RNA extracted from brain tissues was amplified using reverse...
The complete coding sequence of a rabies lyssavirus (RABV) detected in a black bear () was generated. RNA extracted from brain tissues was amplified using reverse transcription followed by tiling PCR sequencing to obtain RABV whole viral genome. Sequencing was performed using an Illumina ISeq 100 instrument.
PubMed: 38349170
DOI: 10.1128/MRA.00821-23 -
MBio Mar 2024Infection with neurotropic viruses may result in changes in host behavior, which are closely associated with degenerative changes in neurons. The lyssavirus genus...
Infection with neurotropic viruses may result in changes in host behavior, which are closely associated with degenerative changes in neurons. The lyssavirus genus comprises highly neurotropic viruses, including the rabies virus (RABV), which has been shown to induce degenerative changes in neurons, marked by the self-destruction of axons. The underlying mechanism by which the RABV degrades neuronal cytoskeletal proteins remains incomplete. In this study, we show that infection with RABV or overexpression of its M protein can disrupt mitochondrial metabolism by binding to Slc25a4. This leads to a reduction in NAD production and a subsequent influx of Ca from the endoplasmic reticulum and mitochondria into the cytoplasm of neuronal cell lines, activating Ca-dependent proteinase calpains that degrade α-tubulin. We further screened the M proteins of different lyssaviruses and discovered that the M protein of the dog-derived RABV strain (DRV) does not degrade α-tubulin. Sequence analysis of the DRV M protein and that of the lab-attenuated RABV strain CVS revealed that the 57th amino acid is vital for M-induced microtubule degradation. We generated a recombinant RABV with a mutation at the 57th amino acid position in its M protein and showed that this mutation reduces α-tubulin degradation and axonal degeneration . This study elucidates the mechanism by which lyssavirus induces neuron degeneration.IMPORTANCEPrevious studies have suggested that RABV (rabies virus, the representative of lyssavirus) infection induces structural abnormalities in neurons. But there are few articles on the mechanism of lyssavirus' effect on neurons, and the mechanism of how RABV infection induces neurological dysfunction remains incomplete. The M protein of lyssavirus can downregulate cellular ATP levels by interacting with Slc25a4, and this decrease in ATP leads to a decrease in the level of NAD in the cytosol, which results in the release of Ca from the intracellular calcium pool, the endoplasmic reticulum, and mitochondria. The presence of large amounts of Ca in the cytoplasm activates Ca-dependent proteases and degrades microtubule proteins. The amino acid 57 of M protein is the key site determining its disruption of mitochondrial metabolism and subsequent neuron degeneration.
Topics: Animals; Dogs; Lyssavirus; Tubulin; NAD; Rabies virus; Rabies; Neurons; Microtubules; Mitochondria; Amino Acids; Nerve Degeneration; Adenosine Triphosphate
PubMed: 38349129
DOI: 10.1128/mbio.02880-23 -
Veterinary World Dec 2023Rabies has been endemic in Bali since 2009, and cases has recently increased. Unfortunately, there is a lack of available vaccines, which hinders the eradication...
BACKGROUND AND AIM
Rabies has been endemic in Bali since 2009, and cases has recently increased. Unfortunately, there is a lack of available vaccines, which hinders the eradication program. This study aimed to investigate the epidemiological and virological aspects of rabies infection in Bali.
MATERIALS AND METHODS
A total of 24 brain samples were collected from rabid dogs in all districts of Bali. The samples were tested using the direct fluorescent antibody (DFA) test and polymerase chain reaction (PCR) to confirm the presence of rabies virus in the samples. Samples with the highest virus content were propagated and then inoculated into BALB/c mice. The brains of dead mice were used to prepare an inoculate cultured in murine neuroblastoma cells. Supernatant-positive viruses representing each district were then reinoculated into eight groups of five BALB/c mice. A brain sample from each dead mouse was tested using DFA and PCR and detected under a fluorescence microscope.
RESULTS
All rabies virus-positive samples collected from rabid dogs in all districts of Bali were positive. Rabies virus was detected by DFA test and PCR and was consistently confirmed in the and studies. BALB/c mice inoculated with the highest viral dilution (105 cells/mL) of culture supernatant showed typical signs of rabies, indicating that the virus could be properly investigated.
CONCLUSION
This study demonstrated a wide epidemiological distribution of rabies in Bali. The obtained virus can be adapted for and studies and can be used to develop a homologous vaccine.
PubMed: 38328353
DOI: 10.14202/vetworld.2023.2446-2450 -
Veterinary World Dec 2023Some Indonesian islands, including Sumatra, Kalimantan, Sulawesi, Java, and East Nusa Tenggara, have endemic rabies. Rabies outbreaks in Bali began from 2008 to 2011 and...
BACKGROUND AND AIM
Some Indonesian islands, including Sumatra, Kalimantan, Sulawesi, Java, and East Nusa Tenggara, have endemic rabies. Rabies outbreaks in Bali began from 2008 to 2011 and continue to occur sporadically. This study aimed to study the molecular analysis and geographical distribution of Indonesian rabies virus (RABV) from 2016 to 2021 and compare to previous periods.
MATERIALS AND METHODS
Virus isolates from 2016 to 2021 were extracted from dog brains and sequenced at the nucleoprotein gene locus. They were compared with data sequences available in the GenBank database. Indonesian RABV from the previous three periods (before 1989, 1997-2003, and 2008-2010) was extracted from the GenBank database. The genetic diversity in this study was based on the N gene of Indonesian RABV.
RESULTS
Asian RABV, which is genetically close to the Indonesian virus, is a virus from China (ASIA-3 cluster) and from the Southeast Asia region, namely, virus isolates from Sarawak and Malaysia and some Cambodian isolates. Rabies virus, which was isolated from the Bali islands, was the new cluster first detected and published in Bali, Indonesia, in 2008, while RABV from West Sumatra Province, which was isolated from 2016 to 2021, was also considered a new cluster that is genetically distant from other clusters in Indonesia.
CONCLUSION
The RABV in Indonesia is divided into five clusters. The isolates from West Sumatra Province from 2016 to 2021 were a new cluster genetically distant from other Indonesian viruses.
PubMed: 38328351
DOI: 10.14202/vetworld.2023.2479-2487 -
ELife Feb 2024Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost...
Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost neuroanatomical techniques based on RNA barcode sequencing have the potential to map circuits at cellular resolution and a brain-wide scale, but existing Sindbis virus-based techniques can only map long-range projections using anterograde tracing approaches. Rabies virus can complement anterograde tracing approaches by enabling either retrograde labeling of projection neurons or monosynaptic tracing of direct inputs to genetically targeted postsynaptic neurons. However, barcoded rabies virus has so far been only used to map non-neuronal cellular interactions in vivo and synaptic connectivity of cultured neurons. Here we combine barcoded rabies virus with single-cell and in situ sequencing to perform retrograde labeling and transsynaptic labeling in the mouse brain. We sequenced 96 retrogradely labeled cells and 295 transsynaptically labeled cells using single-cell RNA-seq, and 4130 retrogradely labeled cells and 2914 transsynaptically labeled cells in situ. We found that the transcriptomic identities of rabies virus-infected cells can be robustly identified using both single-cell RNA-seq and in situ sequencing. By associating gene expression with connectivity inferred from barcode sequencing, we distinguished long-range projecting cortical cell types from multiple cortical areas and identified cell types with converging or diverging synaptic connectivity. Combining in situ sequencing with barcoded rabies virus complements existing sequencing-based neuroanatomical techniques and provides a potential path for mapping synaptic connectivity of neuronal types at scale.
Topics: Animals; Mice; Rabies virus; Neuroanatomy; Neurons; Sequence Analysis, RNA; RNA
PubMed: 38319699
DOI: 10.7554/eLife.87866 -
Open Access Emergency Medicine : OAEM 2024Rabies is a neglected zoonotic disease caused by a virus. It is an acute progressive neurological disease that affects people in many parts of the world, especially in...
Rabies is a neglected zoonotic disease caused by a virus. It is an acute progressive neurological disease that affects people in many parts of the world, especially in low income countries including Somalia and it is always lethal once symptoms appear without immediate post-exposure prophylaxis (PEP). Nearly half of rabies cases occur in children. This case report presents a tragic and unique clinical scenario involving a 14-year-old boy from a rural area in Somalia who presented to our tertiary hospital after a bite from a honey badger. The patient's younger sister, who was also bitten by the same honey badger, sadly succumbed to the disease two weeks prior. This report aims to contribute to the medical literature by highlighting the challenges faced in diagnosing and managing rabies in resource-constrained settings.
PubMed: 38314068
DOI: 10.2147/OAEM.S439996 -
Heliyon Jan 2024Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of...
Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of , to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (T) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.
PubMed: 38293396
DOI: 10.1016/j.heliyon.2024.e24612