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.
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2.
Development of mRNA rabies vaccines Fang, Zixin; Yu, Pengcheng; Zhu, Wuyang
Human vaccines & immunotherapeutics,
12/2024, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing ...the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.Rabies, primarily transmitted to humans by dogs (accounting for 99% of cases). Once rabies occurs, its mortality rate is approximately 100%. Post-exposure prophylaxis (PEP) is critical for preventing the onset of rabies after exposure to rabid animals, and vaccination is a pivotal element of PEP. However, high costs and complex immunization protocols have led to poor adherence to rabies vaccinations. Consequently, there is an urgent need to develop new rabies vaccines that are safe, highly immunogenic, and cost-effective to improve compliance and effectively prevent rabies. In recent years, mRNA vaccines have made significant progress in the structural modification and optimization of delivery systems. Various mRNA vaccines are currently undergoing clinical trials, positioning them as viable alternatives to the traditional rabies vaccines. In this article, we discuss a novel mRNA rabies vaccine currently undergoing clinical and preclinical testing, and evaluate its potential to replace existing vaccines.
As the fourth fundamental circuit element, the memristor may execute computations while storing data. Fracmemristor takes advantage of the fractional calculate’s long-term memory, non-locality, weak ...singularity, and the memristor’s storage–computational integration. Since the physical structure of the fracmemristor is similar to the topology of the ant transfer probability flow in ACO, we propose the fractional-order memristive ant colony algorithm (FMAC), which uses the fracmemristor physical system to record the probabilistic transfer information of the nodes that the ant will crawl through in the future and pass it to the current node of the ant, so that the ant acquires the ability to predict the future transfer. After instigating the optimization capabilities with TSP, we discovered that FMAC is superior to PACO-3opt, the best integer-order ant colony algorithm currently available. FMAC operates substantially more quickly than the fractional-order memristor ant colony algorithm due to the transfer probability prediction module based on the physical fracmemristor system (FACA).
Objective:
This study aimed to enhance the current understanding of the epidemiologic characteristics, laboratory diagnostic levels, and changes in pathogenic populations of rabies in China by ...studying the status of the human rabies epidemic in China from 2015-2021 and provide useful information for guiding rabies disease prevention and control strategies.
Methods:
We analyzed the incidence, distribution, and laboratory testing of human rabies in mainland China using statutory surveillance data from 2015-2021. Based on a literature review, the study summarizes the recent updates of the rabies virus population in each province based on previous monitoring.
Results:
A total of 3032 rabies cases were reported in China from 2015-2021, with a year-after-year decrease in the total number of cases. Most of the cases (75.19%) were distributed in Hunan, Henan, Guangxi, Guizhou, Hubei, Yunnan, Jiangsu, Anhui, Guangdong, and Sichuan, with 13 counties (districts) reporting > 50 cases in 7 years. The number of reported counties (districts) decreased from 512 in 2015 to 116 in 2021. Farmers accounted for most of the cases (73%), and the highest proportion of cases (54.62%) occurred in individuals 50-75 years of age. No changes in endemic populations were detected in China. The laboratory diagnosis rate of cases increased from 4.74% in 2015 to 22.93% in 2021.
Conclusions:
The rabies epidemic in China decreased steadily from 2015-2021, with a marked contraction in the geographic scope. In the future it will be necessary to continue to carry out large-scale dog immunization and strengthen the surveillance and laboratory diagnosis of rabies.
Background The mortality of humans due to rabies in China has been declining in recent years, but it is still a significant public health problem. According to the global framework, China strives to ...achieve the goal of eliminating human rabies before 2030. Methods We reviewed the epidemiology of human deaths from rabies in mainland China from 2004 to 2018. We identified high risk regions, age and occupational groups, and used a continuous deterministic susceptibility-exposure-infection-recovery (SEIR) model with periodic transmission rate to explore seasonal rabies prevalence in different human populations. The SEIR model was used to simulate the data of human deaths from rabies reported by the Chinese Center for Disease Control and Prevention (China CDC). We calculated the relative transmission intensity of rabies from canines to different human groups, and they provided a reliable epidemiological basis for further control and prevention of human rabies. Results Results showed that human deaths from rabies exhibited regional differences and seasonal characteristics in mainland China. The annual human death from rabies in different regions, age groups and occupational groups decreased steadily across time. Nevertheless, the decreasing rates and the calculated R.sub.0 s of canines of various human groups were different. The transmission intensity of rabies from canines to human populations was the highest in the central regions of China, in people over 45 years old, and in farmers. Conclusions Although the annual cases of human deaths from rabies have decreased steadily since 2007, the proportion of human deaths from rabies varies with region, age, gender, and occupation. Further enhancement of public awareness and immunization status in high-risk population groups and blocking the transmission routes of rabies from canines to humans are necessary. The concept of One Health should be abided and human, animal, and environmental health should be considered simultaneously to achieve the goal of eradicating human rabies before 2030.
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Seadornavirus is a genus of viruses in the family Reoviridae, which consists of Banna virus, Kadipiro virus, and Liao ning virus. Banna virus is considered a potential pathogen for zoonotic diseases. ...Here, we describe a newly discovered Seadornavirus isolated from mosquitos (Culex tritaeniorhynchus) in Yunnan Province, China, which is related to Banna virus, and referred to as Mangshi virus.
The Mangshi virus was isolated by cell culture in Aedes albopictus C6/36 cells, in which it replicated and caused cytopathic effects, but not in mammalian BHK-21 or Vero cells. Polyacrylamide gel analysis revealed a genome consisting of 12 segments of double-stranded RNA, with a "6-4-2" pattern in which the migrating bands were different from those of the Banna virus. Complete genome sequencing was performed by full-length amplification of cDNAs. Sequence analysis showed that seven highly conserved nucleotides and three highly conserved nucleotides were present at the ends of the 5'- and 3'-UTRs in each of 12 genome segments. The amino acid identities of Mangshi virus shared with Balaton virus varied from 27.3% (VP11) to 72.3% (VP1) with Banna virus varying from 18.0% (VP11) to 63.9% (VP1). Phylogenetic analysis based on amino acid sequences demonstrated that Mangshi virus is a member of the genus Seadornavirus and is most closely related to, but distinct from, Balaton virus and Banna virus in the genus Seadornavirus of the family Reoviridae.
Mangshi virus isolated from mosquitoes (C. tritaeniorhynchus) was identified as a newly discovered virus in the genus Seadornavirus and is phylogenetically close to Banna virus, suggesting that there is genetic diversity of seadornaviruses in tropical and subtropical areas of Southeast Asia.
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Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like ...receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models.
A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP.
HDCV combined with CpG ODN (HDCV-CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV-1.25 μg CpG or HDCV-5 μg CpG increased the levels of RVNA. In particular, 5 μg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 μg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV-CpG survived, while the survival rate of mice immunized with HDCV alone was 30%.
The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.
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Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis diseases worldwide. China has a long history of high prevalence of Japanese encephalitis, with thousands of cases ...reported annually and incidence rates often exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence of these pandemics has almost been unique, placing a heavy burden on the Chinese health authorities. However, the introduction of vaccines, developed in China, combined with an intensive vaccination program initiated during the 1970s, as well as other public health interventions, has dramatically decreased the incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less readily accessible areas of China, changes to agricultural practices designed to reduce chances of mosquito bites as well as mosquito population densities have also been proven effective in reducing local JE incidence. This unprecedented public health achievement has saved many lives and provided valuable experience that could be directly applicable to the control of vector-borne diseases around the world. Here, we review and discuss strategies for promotion and expansion of vaccination programs to reduce the incidence of JE even further, for the benefit of health authorities throughout Asia and, potentially, worldwide.
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Abstract Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine ...(LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.
During July 2015, physicians at a hospital in Beijing, China, diagnosed rabies in 2 patients who had each received a kidney from a common organ donor who had died from acute progressive encephalitis ...of unknown cause. The patients had rabies incubation periods of 42 and 48 days. Altered mental status developed in both patients and progressively worsened to deep coma within 80 days after transplantation; both patients died. Two other transplant recipients received corneas but remained well after receiving timely rabies prophylaxis. An effective regulatory system for testing donors should be implemented to decrease the occurrence of donor-derived infectious diseases. In addition, health education should be improved to enhance public awareness of transplant-associated infectious diseases. Transplant recipients and other persons with exposure to organs or tissues from donors with rabies must be provided consistent health monitoring and follow-up, including rabies postexposure prophylaxis; any remaining organs and tissues must be quarantined and not transplanted.
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