-
Biologicals : Journal of the... Jul 2022We have obtained an attenuated rabies virus CTN181-3. In this paper, we make a comprehensive studies on CTN181-3. CTN181-3 showed no pathogenicity by i. c. or o. i....
We have obtained an attenuated rabies virus CTN181-3. In this paper, we make a comprehensive studies on CTN181-3. CTN181-3 showed no pathogenicity by i. c. or o. i. inoculation in 3-week-old mice, lower pathogenic in 2-week-old mice, and no virulence by o. i. inoculation in 8-week-old golden hamsters. CTN181-3 showed high immunogenicity, which produced high level neutralizing antibodies, 100% sero-conversation and >5.0 IU/ml GMT by one dose i. m. or o. i. vaccination in mice and golden hamsters. Cellular immune response by one dose i. m. or o. i. inoculation was detected. Especially in PEP, reduced dose of vaccination resulted in 50% (one dose) and 100% (2 doses) protections in golden hamsters. Molecular basis of the attenuation indicated that eight substitutions compared to its parental virus strain CTN-1, among them the two substitutions at the G276 (Leu→Val) and L1496 (Met→Trp) were the critical attenuated site. The phenotypic and genotypic characteristics of CTN181-3 were highly stable, no reversion was occurred when the virus was multiple passaged in suckling mice brains, guinea pig submandibular glands or BSR/Vero cell cultures. The gene homology compared to the Chinese rabies isolates showed much higher than rabies vaccine strains used in China, suggesting CTN181-3 is a promising and suitable oral rabies vaccine candidate strain.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Cricetinae; Guinea Pigs; Mesocricetus; Mice; Rabies; Rabies Vaccines; Rabies virus; Vero Cells
PubMed: 35786353
DOI: 10.1016/j.biologicals.2022.06.004 -
ACS Nano Mar 2022T lymphocyte infiltration with immunotherapy potentially suppresses most devastating brain tumors. However, local immune privilege and tumor heterogeneity usually limit...
T lymphocyte infiltration with immunotherapy potentially suppresses most devastating brain tumors. However, local immune privilege and tumor heterogeneity usually limit the penetration of immune cells and therapeutic agents into brain tumors, leading to tumor recurrence after treatment. Here, a rabies virus glycoprotein (RVG)-camouflaged gold yarnball (RVG@GY) that can boost the targeting efficiency at a brain tumor dual hierarchy- and RVG-mediated spinal cord transportation, facilitating the decrease of tumor heterogeneity for T cell infiltration, is developed. Upon magnetoelectric irradiation, the electron current generated on the GYs activates the electrolytic penetration of palbociclib-loaded dendrimer (Den[Pb]) deep into tumors. In addition, the high-density GYs at brain tumors also induces the disruption of cell-cell interactions and T cell infiltration. The integration of the electrolytic effects and T cell infiltration promoted by drug-loaded RVG@GYs deep in the brain tumor elicits sufficient T cell numbers and effectively prolongs the survival rate of mice with orthotopic brain tumors.
Topics: Animals; Brain Neoplasms; Glycoproteins; Gold; Mice; Rabies virus; T-Lymphocytes
PubMed: 35225594
DOI: 10.1021/acsnano.1c09601 -
The Journal of General Virology Jul 2021Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated...
Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated genes (ISGs), among which the family of genes of IFN-induced protein with tetratricopeptide repeats (Ifits) are prominent representatives. Herein, we demonstrated that the mRNA and protein levels of Ifit1, Ifit2 and Ifit3 were highly increased in cultured cells and mouse brains after RABV infection. Recombinant RABV expressing Ifit3, designated rRABV-Ifit3, displayed a lower pathogenicity than the parent RABV in C57BL/6 mice after intramuscular administration, and Ifit3-deficient mice exhibited higher susceptibility to RABV infection and higher mortality during RABV infection. Moreover, compared with their individual expressions, co-expression of Ifit2 and Ifit3 could more effectively inhibit RABV replication . These results indicate that murine Ifit3 plays an essential role in restricting the replication and reducing the pathogenicity of RABV. Ifit3 acts synergistically with Ifit2 to inhibit RABV replication, providing further insight into the function and complexity of the Ifit family.
Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis Regulatory Proteins; Brain; Cell Line; Female; Humans; Immunity, Innate; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; RNA, Messenger; RNA-Binding Proteins; Rabies; Rabies virus; Transcriptome; Viral Load; Virus Replication
PubMed: 34269675
DOI: 10.1099/jgv.0.001619 -
International Journal of Molecular... Apr 2023Rabies is a highly fatal disease, and it is vital to find effective ways to manage and control infection. There is a need for new effective antiviral drugs that are...
Rabies is a highly fatal disease, and it is vital to find effective ways to manage and control infection. There is a need for new effective antiviral drugs that are particularly effective treatments for rabies. Deoxynivalenol (DON) is known mainly for its toxicity, but at the molecular level, it can inhibit RNA and DNA replication, and there is increasing evidence that different doses of DON have a positive effect on inhibiting virus replication. Based on this, we evaluated the effect of DON on inhibiting the rabies virus in vitro. The inhibitory effect of DON on rabies virus activity was dose- and time-dependent, and 0.25 μg/mL of DON could inhibit 99% of rabies virus activity within 24 h. Furthermore, DON could inhibit the adsorption, entry, replication, and release of rabies virus but could not inactivate the virus. The inhibitory effect of DON on rabies virus may be achieved by promoting apoptosis. Our study provides a new perspective for the study of anti-rabies virus and expands the direction of action of mycotoxins.
Topics: Mycotoxins; Rabies virus; Trichothecenes; Virus Replication
PubMed: 37175500
DOI: 10.3390/ijms24097793 -
Clinical Infectious Diseases : An... Sep 2023All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM)...
Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.
All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.
Topics: Animals; Humans; Rabies Vaccines; Rabies virus; Post-Exposure Prophylaxis; Injections, Intramuscular; Rabies; Antibodies, Neutralizing; Injections, Intradermal; Antibodies, Viral
PubMed: 37337899
DOI: 10.1093/cid/ciad304 -
Journal of the American Veterinary... Jan 2020To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether...
OBJECTIVE
To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether a standardized approach to specimen selection for RABV characterization could enhance detection of a sentinel event in virus dissemination among bats.
SAMPLE
United States public health rabies surveillance system data collected in January 2010 through December 2015.
PROCEDURES
The number of rabies-tested bats for which species was reported and the number of RABV-positive samples for which virus characterization would likely provide information regarding introduction of novel RABV variants and translocation and host-shift events were calculated. These specimens were designated as specimens of epizootiological importance (SEIs). Additionally, the estimated test load that public health laboratories could expect if all SEIs underwent RABV characterization was determined.
RESULTS
Species was reported for 74,928 of 160,017 (47%) bats submitted for rabies testing. Identified SEIs were grouped in 3 subcategories, namely nonindigenous bats; bats in southern border states, Florida, Puerto Rico, and the US Virgin Islands; and bats of species that are not commonly found to be inflected with RABV. Annually, 692 (95% CI, 600 to 784) SEIs were identified, of which only 295 (95% CI, 148 to 442) underwent virus characterization. Virus characterization of all SEIs would be expected to increase public health laboratories' overall test load by 397 (95% CI, 287 to 506) samples each year.
CONCLUSIONS AND CLINICAL RELEVANCE
Species identification and RABV characterization may aid detection of a sentinel event in bat RABV dissemination. With additional resources, RABV characterization of all SEIs as a standardized approach to testing could contribute to knowledge of circulating bat RABV variants.
Topics: Animals; Chiroptera; Florida; Puerto Rico; Rabies; Rabies virus; United States
PubMed: 31841089
DOI: 10.2460/javma.256.1.77 -
Emerging Microbes & Infections Dec 2024During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance...
During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within or genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both and and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) - follicular helper T (Tfh) cells - germinal centre (GC) / memory B cells (MBCs) - long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the and genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.
Topics: Cats; Dogs; Humans; Animals; Mice; Rabies virus; Rabies Vaccines; Immunity, Humoral; Cat Diseases; Antibodies, Viral; Dog Diseases; Adenoviridae
PubMed: 38164714
DOI: 10.1080/22221751.2023.2300461 -
Archives of Virology Nov 2022Genetic relationships between rabies virus (RABV) isolates recovered from dogs, jackals, and cattle in Georgia and their closest relatives were investigated by comparing...
Genetic relationships between rabies virus (RABV) isolates recovered from dogs, jackals, and cattle in Georgia and their closest relatives were investigated by comparing their nucleoprotein (N) gene sequences. Multiple isolates from dogs and cattle were found to share identical N gene sequences, indicating a risk of dog-to-cattle rabies transmission in Georgia. Exhibiting population-selective sweeps, expansion, and genetic recombination, evolutionary analysis of Georgian RABV isolates (all belonging to the cosmopolitan clade) and isolates from Russia, Turkey, and elsewhere provided further evidence for coinfections with different rabies virus strains and transborder transmission.
Topics: Animals; Cattle; Dogs; Nucleoproteins; Phylogeny; Rabies; Rabies virus; Georgia (Republic)
PubMed: 35913651
DOI: 10.1007/s00705-022-05550-3 -
PLoS Neglected Tropical Diseases Jul 2023Rabies is the oldest fatal zoonotic disease recognised as a neglected tropical disease and is caused by an RNA virus belonging to the genus Lyssavirus, family...
BACKGROUND
Rabies is the oldest fatal zoonotic disease recognised as a neglected tropical disease and is caused by an RNA virus belonging to the genus Lyssavirus, family Rhabdoviridae.
METHODOLOGY/PRINCIPAL FINDINGS
A deep molecular analysis was conducted on full-length nucleoprotein (N) gene and whole genome sequences of rabies virus from 37 animal brain samples collected between 2012 and 2017 to study the circulation of rabies virus (RABV) variants. The overall aim was to better understand their distribution in Moldova and north-eastern Romania. Both Sanger and high throughput sequencing on Ion Torrent and Illumina platforms were performed. Phylogenetic analysis of the RABV sequences from both Moldova and Romania revealed that all the samples (irrespective of the year of isolation and the species) belonged to a single phylogenetic group: north-eastern Europe (NEE), clustering into three assigned lineages: RO#5, RO#6 and RO#7.
CONCLUSIONS/SIGNIFICANCE
High throughput sequencing of RABV samples from domestic and wild animals was performed for the first time for both countries, providing new insights into virus evolution and epidemiology in this less studied region, expanding our understanding of the disease.
Topics: Animals; Rabies virus; Phylogeny; Romania; Moldova; Rabies; Whole Genome Sequencing
PubMed: 37410714
DOI: 10.1371/journal.pntd.0011446 -
Zoonoses and Public Health Mar 2020Bats are essential to the global ecosystem, but their ability to harbour a range of pathogens has been widely discussed, as well as their role in the emergence and...
Bats are essential to the global ecosystem, but their ability to harbour a range of pathogens has been widely discussed, as well as their role in the emergence and re-emergence of infectious diseases. This paper describes the first report of coinfection by two zoonotic agents, rabies virus (RABV) and the fungus Histoplasma suramericanum in a bat. The bat was from the Molossus molossus species, and it was found during the daytime in the hallway of a public psychiatric hospital in a municipality in São Paulo State, southeastern Brazil. RABV infection was diagnosed by the direct fluorescent antibody test and mouse inoculation test. The fungus was isolated by in vitro culture. Both diagnoses were confirmed by molecular techniques. Phylogenetic analysis showed that the fungus isolate had proximity to H. suramericanum in the Lam B clade, while the RABV isolate was characterized in the Lasiurus cinereus lineage. Since the M. molossus bat was found in a peri-urban transition area (urban/peri-urban), the possibility of cross-species transmission of this RABV lineage becomes more plausible, considering that this scenario may provide shelter for both M. molossus and L. cinereus. These are relevant findings since there has been an increase in bat populations in urban and peri-urban areas, particularly due to environmental modifications and anthropogenic impacts on their habitat. Thus, the detection of two zoonotic agents in a bat found in a public hospital should raise awareness regarding the importance of systematic surveillance actions directed towards bats in urban areas.
Topics: Animals; Brazil; Chiroptera; Histoplasma; Histoplasmosis; Phylogeny; Population Surveillance; Rabies; Rabies virus
PubMed: 31750629
DOI: 10.1111/zph.12663