RESUMO
This study was a randomized, parallel-controlled of homologous vaccines with different immune procedure research to evaluate the immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals. 240 subjects aged ≤ 20ã21-50ã≥51 y were randomly divided into 2 groups (1:1), Zagreb 2-1-1 regimen receivers as experimental group and Essen 5 regimen receivers as controlled group. Researchers collected venous blood of each subject before vaccine injection and on the day 7, 14, 42, 180, 365 after first dose. The immunogenicity and immune persistence was assessed by neutralizing antibody. The positive rate of neutralizing antibody in experimental group was 14.53% on the 7th day, and raised to 100% on the 14th day. It showed no significant difference between experimental and controlled group (P>0.05). Either in experimental or controlled group, GMC of neutralizing antibody was up to the peak on the 14th day, and it showed no significant difference between two groups (P>0.05). On the 42nd day, the antibody positive rate remained 100% with both Zagreb 2-1-1 and Essen 5 regimens, and the GMC of antibodies also remained high level. Then, on the 180th and 365th day with both regimens, the GMC of antibodies dropped dramatically, although it remained above the protective level of 0.5 IU/ml, the positive rates dropped to 84.40% and 84.11% (on the 180th day), and 61.29% and 58.62% (on the 365th day). Rabies vaccine injected by Zagreb 2-1-1 regimen can produce neutralizing antibody fastly and perdurably.Registration: ClinicalTrials.gov #NCT01821911and NCT01827917.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina Antirrábica , Raiva , Humanos , Vacina Antirrábica/imunologia , Vacina Antirrábica/administração & dosagem , Anticorpos Neutralizantes/sangue , Masculino , Anticorpos Antivirais/sangue , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Raiva/prevenção & controle , Raiva/imunologia , Adolescente , Imunogenicidade da Vacina , Voluntários Saudáveis , China , Idoso , Vacinação/métodosRESUMO
Animal rabies is a potentially fatal infectious disease in mammals, especially dogs. Currently, the number of rabies cases in pet dogs is increasing in several regions of Thailand. However, no passive postexposure prophylaxis (PEP) has been developed to combat rabies infection in animals. As monoclonal antibodies (MAbs) are promising biological therapies for postinfection, we developed a canine-neutralizing MAb against rabies virus (RABV) via the single-chain variable fragment (scFv) platform. Immunized phage-displaying scFv libraries were constructed from PBMCs via the pComb3XSS system. Diverse canine VHVLκ and VHVLλ libraries containing 2.4 × 108 and 1.3 × 106 clones, respectively, were constructed. Five unique clones that show binding affinity with the RABV glycoprotein were then selected, of which K9RABVscFv1 and K9RABVscFv16 showed rapid fluorescent foci inhibition test (RFFIT) neutralizing titers above the human protective level of 0.5 IU/ml. Finally, in silico docking predictions revealed that the residues on the CDRs of these neutralizing clones interact mainly with similar antigenic sites II and III on the RABV glycoprotein. These candidates may be used to develop complete anti-RABV MAbs as a novel PEP protocol in pet dogs and other animals.
Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vírus da Raiva , Raiva , Anticorpos de Cadeia Única , Animais , Cães , Vírus da Raiva/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/genética , Raiva/prevenção & controle , Raiva/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Biblioteca de Peptídeos , Doenças do Cão/imunologia , Doenças do Cão/virologia , Doenças do Cão/prevenção & controle , Doenças do Cão/terapia , Simulação de Acoplamento Molecular , Técnicas de Visualização da Superfície Celular , ImunizaçãoRESUMO
Rabies is endemic in Sudan with continuing outbreaks occurring annually, the most common animals affected are dogs, followed by goats and equids. This work focused on equid rabies, to elucidate the current situation of the disease through analysis of reports of equid rabies outbreaks in Sudan during 2010-2022 supported by laboratory confirmation of the disease. During the study period, 66 animals were affected during 35 equid rabies outbreaks. The highest incidences were found in Al Gezira (30.3%), followed by Darfur (24.2%) and Kordofan (15.2%). The highest incidence rate was observed during 2018 (33.3%), followed by 2015 (16.7%). Within seasons, the highest incidence rate was reported during October - December (33.3%), followed by July - September (30.3%). Chi-square analysis revealed a significant correlation between rabid animals and year, season, and state. Wald statistics demonstrated that year and season had a significant association with the disease. Virus antigen was identified (72.2%) in brain tissues using the fluorescent antibody test. Viral nucleic acid was amplified (n = 6) with a reverse transcriptase polymerase chain reaction assay.Contribution: As equids are kept in close contact with humans and other animals in the country, according to the present investigation, equid rabies in Sudan is a potential public health concern, emphasising the importance of implementing effective control measures.
Assuntos
Equidae , Doenças dos Cavalos , Raiva , Animais , Sudão/epidemiologia , Raiva/epidemiologia , Raiva/veterinária , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/virologia , Surtos de Doenças/veterinária , Incidência , Cavalos , Estações do AnoRESUMO
Responsável pelas ações de vigilância e promoção à saúde, documentação, ensino e divulgação científica.
Assuntos
Raiva , Promoção da SaúdeRESUMO
Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses.
Assuntos
Microscopia Crioeletrônica , Vírus da Raiva , Vírion , Vírus da Raiva/ultraestrutura , Vírus da Raiva/química , Vírion/ultraestrutura , Animais , RNA Viral/genética , RNA Viral/metabolismo , Tomografia com Microscopia Eletrônica , Modelos Moleculares , Nucleocapsídeo/ultraestrutura , Nucleocapsídeo/metabolismo , Nucleocapsídeo/química , Raiva/virologia , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/metabolismo , Proteínas da Matriz Viral/ultraestrutura , Proteínas da Matriz Viral/genéticaRESUMO
BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.
Assuntos
Raiva , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária , China/epidemiologia , Humanos , Animais , Cães , Incidência , Masculino , Feminino , Adolescente , Criança , Adulto , Pessoa de Meia-Idade , Estações do Ano , Pré-Escolar , Adulto Jovem , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Doenças do Cão/prevenção & controle , Lactente , Idoso , Profilaxia Pós-Exposição , Vacina Antirrábica/administração & dosagemRESUMO
Rabies, caused by the Rabies virus (RABV), is a highly fatal zoonotic disease. Existing rabies vaccines have demonstrated good immune efficacy, but the complexity of immunization procedures and high cost has impeded the elimination of RABV, particularly in the post-COVID-19 era. There is a pressing need for safer and more effective rabies vaccines that streamline vaccination protocols and reduce expense. To meet this need, we have developed a potential rabies vaccine candidate called ALVAC-RABV-VLP, utilizing CRISPR/Cas9 gene editing technology. This vaccine employs a canarypox virus vector (ALVAC) to generate RABV virus-like particles (VLPs). In mice, a single dose of ALVAC-RABV-VLP effectively activated dendritic cells (DCs), follicular helper T cells (Tfh), and the germinal centre (GC)/plasma cell axis, resulting in durable and effective humoral immune responses. The survival rate of mice challenged with lethal RABV was 100%. Similarly, in dogs and cats, a single immunization with ALVAC-RABV-VLP elicited a stronger and longer-lasting antibody response. ALVAC-RABV-VLP induced superior cellular and humoral immunity in both mice and beagles compared to the commercial inactivated rabies vaccine. In conclusion, ALVAC-RABV-VLP induced robust protective immune responses in mice, dogs and cats, offering a novel, cost-effective, efficient, and promising approach for herd prevention of rabies.
Assuntos
Anticorpos Antivirais , Vacina Antirrábica , Vírus da Raiva , Raiva , Vacinas de Partículas Semelhantes a Vírus , Animais , Cães , Vacina Antirrábica/imunologia , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/genética , Camundongos , Vírus da Raiva/imunologia , Vírus da Raiva/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Raiva/prevenção & controle , Raiva/imunologia , Gatos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vírus da Varíola dos Canários/imunologia , Vírus da Varíola dos Canários/genética , Vetores Genéticos/genética , Feminino , Células Dendríticas/imunologia , Imunidade Humoral , Sistemas CRISPR-Cas , Camundongos Endogâmicos BALB CRESUMO
Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.
Assuntos
Fator 88 de Diferenciação Mieloide , NF-kappa B , Vírus da Raiva , Transdução de Sinais , Receptor 7 Toll-Like , Receptor 7 Toll-Like/metabolismo , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Vírus da Raiva/patogenicidade , Vírus da Raiva/imunologia , Camundongos , NF-kappa B/metabolismo , Linhagem Celular , Interleucina-6/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Raiva/virologia , Raiva/metabolismo , Raiva/imunologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Inflamação/metabolismoRESUMO
Human rabies transmitted by dogs still kills thousands of people each year worldwide. Dog bites are common in the city of Beni (Democratic Republic of Congo), which shows low rabies vaccination coverage. This study aimed to determine the factors associated with the rabies vaccination status of dogs. A cross-sectional analytical study was conducted in the town of Beni among dog owners, during a household survey selected using a multistage sampling. The information sought concerned the knowledge and characteristics of the dog owners as well as the vaccination status of these dogs. Logistic regression was used to investigate associations between the vaccination status of the dogs and the main independent factors. Rabies vaccination coverage in Beni was 26% (95% confidence interval [CI]: 22% - 30%). The main factors associated with the rabies vaccination status of the dog were primary education level of household head (adjusted odds ratio [aOR]:4.8; 95% CI: 1.2- 19.8); university education level of household head (aOR: 5.9; 95% CI: 1.6-22); perceived rabies severity (aOR: 44. 4; 95% CI: 10.4-188), having more than one dog in the household (aOR: 2.6; 95% CI: 1.6-4.3); age range 7-12 months (aOR: 0.2; 95% CI: 0.1-0.6) and confined dog breeding (aOR: 3.9; 95% CI: 1.1-14.9). The low vaccination coverage in Beni requires mass vaccination campaigns against canine rabies targeting the dog owners with low education levels, those raising more than one dog, with stray dogs or dogs less than 12 months old.
Assuntos
Doenças do Cão , Vacina Antirrábica , Raiva , Cães , Animais , Raiva/prevenção & controle , Raiva/veterinária , Raiva/epidemiologia , Doenças do Cão/prevenção & controle , Doenças do Cão/epidemiologia , Estudos Transversais , Vacina Antirrábica/administração & dosagem , Masculino , Feminino , Humanos , República Democrática do Congo/epidemiologia , Vacinação/veterinária , Vacinação/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Características da Família , Conhecimentos, Atitudes e Prática em Saúde , Cobertura Vacinal/estatística & dados numéricosRESUMO
INTRODUCTION: Rabies is a fatal infectious disease, that poses a major public health threat in developing countries. With an annual death toll of approximately 59,000, more than half of which are children, an urgent need exists for a safe, affordable, and effective preventive measure against rabies virus infection. METHODOLOGY: A recombinant rabies vaccine called Ad5-dRVG was constructed by introducing two copies of the rabies virus glycoprotein into a human adenoviral vector. Virus-neutralizing assays and virus challenge experiments were employed to evaluate the Ad5-dRVG vaccine. RESULTS: Our findings demonstrate that a single dose of Ad5-dRVG, administered either intramuscularly or orally, elicited significantly stronger immune responses than Ad5-RVG. Moreover, both vaccines provided complete protection in mice. Notably, the vaccine exhibited remarkable efficacy even at low doses, suggesting potential cost reduction in production. CONCLUSIONS: The development of the Ad5-dRVG recombinant rabies vaccine represents a significant advancement in rabies prevention. Its enhanced immunogenicity, demonstrated efficacy and potential cost savings make it a promising candidate for widespread use.
Assuntos
Vetores Genéticos , Glicoproteínas , Vacina Antirrábica , Vírus da Raiva , Raiva , Vacinas Sintéticas , Animais , Vacina Antirrábica/imunologia , Vacina Antirrábica/genética , Vacina Antirrábica/administração & dosagem , Raiva/prevenção & controle , Raiva/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/administração & dosagem , Glicoproteínas/imunologia , Glicoproteínas/genética , Camundongos , Vírus da Raiva/imunologia , Vírus da Raiva/genética , Feminino , Anticorpos Antivirais/sangue , Adenoviridae/genética , Camundongos Endogâmicos BALB C , Injeções Intramusculares , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Humanos , Modelos Animais de Doenças , Administração Oral , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Eficácia de VacinasRESUMO
Rabies is a neglected disease primarily related to dog-mediated transmission to humans. Accurate dog demographic and dynamic data are essential for effectively planning and evaluating population management strategies when designing interventions to prevent rabies. However, in Thailand, longitudinal survey data regarding dog population size are scarce. A school-based participatory research (SBPR) approach was conducted to survey owned dogs for one year in four high-risk provinces (Chiang Rai, Surin, Chonburi, and Songkhla) of Thailand, aiming to understand dog population dynamics and raise awareness about rabies. 'Pupify' mobile application was developed to collect data on dog population and observe the long-term population dynamics in this study. At the end of the data collection period, telephone interviews were conducted to gain insight into contextual perceptions and awareness regarding both animal and human rabies, as well as the social responsibility of dog owners in disease prevention and control. Among 303 high school students who registered in our study, 218 students reported at least one update of their dog information throughout the one-year period. Of 322 owned dogs from our survey, the updates of dog status over one year showed approximately 7.5 newborns per 100-dog-year, while deaths and missing dogs were 6.2 and 2.7 per 100-dog-year, respectively. The male to female ratio was approximately 1.8:1. Twenty-three students (10%) voluntarily participated and were interviewed in the qualitative study. The levels of rabies awareness and precautions among high-school students were relatively low. The high dropout rate of the survey was due to discontinuity in communication between the researcher and the students over the year. In conclusion, this study focused on using the SBPR approach via mobile application to collect data informing dog population dynamics and raising awareness regarding rabies in Thailand Other engaging platforms (e.g. Facebook, Instagram, Twitter, and other popular applications) is necessary to enhance communication and engagement, thereby sustaining and maintaining data collection. Further health education on rabies vaccination and animal-care practices via social media platforms would be highly beneficial. For sustainable disease control, engaging communities to raise awareness of rabies and increase dog owners' understanding of their responsibilities should be encouraged.
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Doenças do Cão , Conhecimentos, Atitudes e Prática em Saúde , Dinâmica Populacional , Raiva , Cães , Raiva/prevenção & controle , Raiva/epidemiologia , Raiva/veterinária , Animais , Tailândia/epidemiologia , Humanos , Masculino , Feminino , Doenças do Cão/prevenção & controle , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Instituições Acadêmicas , Adolescente , Pesquisa Participativa Baseada na Comunidade , Estudantes/psicologia , Inquéritos e QuestionáriosRESUMO
During the period 2013-2023, 917 cases of rabies among animals were registered in the Republic of Kazakhstan. Out of these, the number of cases in farm animals amounted to 515, in wild animals to 50 and in pets to 352. Data on rabies cases were obtained from the Committee for Veterinary Control and Supervision of Kazakhstan, as well as during expeditionary trips. This research was carried out to demonstrate the use of modern information and communication technologies, geospatial analysis technologies in particular, to identify and visualize spatio-temporal patterns of rabies emergence among different animal species in Kazakhstan. We also aimed to predict an expected number of cases next year based on time series analysis. Applying the 'space-time cube' technique to a time series representingcases from the three categories of animals at the district-level demonstrated a decreasing trend of incidence in most of the country over the study period. We estimated the expected number of rabies cases for 2024 using a random forest model based on the space-time cube in Arc-GIS. This type of model imposes only a few assumptions on the data and is useful when dealing with time series including complicated trends. The forecast showed that in most districts of Kazakhstan, a total of no more than one case of rabies should beexpected, with the exception of certain areas in the North and the East of the country, where the number of cases could reach three. The results of this research may be useful to the veterinary service in mapping the current epidemiological situation and in planning targeted vaccination campaigns among different categories of animals.
Assuntos
Raiva , Análise Espaço-Temporal , Raiva/epidemiologia , Raiva/veterinária , Cazaquistão/epidemiologia , Animais , Animais Selvagens/virologia , Animais Domésticos/virologia , Sistemas de Informação Geográfica , Incidência , CãesRESUMO
BACKGROUND: Emergency departments (ED) are frequently visited after suspected rabies exposure (SRE) and the potential need for rabies post-exposure prophylaxis (R-PEP). However, data on the number of visits, patients' demographics, travel history and the medical treatment is still rare. Therefore, the aim of this study was to assess the number of R-PEP and the appropriateness of medical management including wound treatment, vaccination regime and immunoglobulin application following SRE in a university hospital ED. METHOD: We conducted a monocentric retrospective observational study on emergency patients treated in the ED of the LMU University Hospital, Ludwig-Maximilians-University Munich, Germany, between June 1st, 2023 and January 31st, 2024. Patients requiring post-exposure prophylaxis due to SRE abroad or in Germany were included. Demographic data, travel history, clinical findings, wound treatment, and R-PEP vaccination regimen were recorded. RESULTS: During the observation period of 245 days 43 patients presented to our ED for R-PEP. There was a total of 51 presentation appointments, as 5 patients returned for further treatment. Most patients (27, 52.9 %) presented at the ED on a Saturday, Sunday, or a public holiday. 17 (39.5 %) patients had a category II exposure, and 26 (60.5 %) had a category III exposure. In our ED, there were 28 (55.0 %) active vaccinations and 23 (45.0 %) both active and passive vaccinations. CONCLUSIONS: Our data show that patients frequently present for R-PEP in ED. Therefore, there is a high need for education on indication for R-PEP and for implementation of precise R-PEP treatment guidelines in daily clinical practice.
Assuntos
Serviço Hospitalar de Emergência , Profilaxia Pós-Exposição , Vacina Antirrábica , Raiva , Humanos , Raiva/prevenção & controle , Estudos Retrospectivos , Masculino , Feminino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/uso terapêutico , Alemanha , Idoso , Adulto Jovem , Adolescente , Viagem , Vacinação/estatística & dados numéricos , CriançaRESUMO
Rabies is a lethal zoonotic disease that threatens human health. As the only viral surface protein, the rabies virus (RABV) glycoprotein (G) induces main neutralizing antibody (Nab) responses; however, Nab titre is closely correlated with the conformation of G. Virus-like particles (VLP) formed by the co-expression of RABV G and matrix protein (M) improve retention and antigen presentation, inducing broad, durable immune responses. RABV nucleoprotein (N) can elicit humoral and cellular immune responses. Hence, we developed a series of nucleoside-modified RABV mRNA vaccines encoding wild-type G, soluble trimeric RABV G formed by an artificial trimer motif (tG-MTQ), membrane-anchored prefusion-stabilized G (preG). Furthermore, we also developed RABV VLP mRNA vaccine co-expressing preG and M to generate VLPs, and VLP/N mRNA vaccine co-expressing preG, M, and N. The RABV mRNA vaccines induced higher humoral and cellular responses than inactivated rabies vaccine, and completely protected mice against intracerebral challenge. Additionally, the IgG and Nab titres in RABV preG, VLP and VLP/N mRNA groups were significantly higher than those in G and tG-MTQ groups. A single administration of VLP or VLP/N mRNA vaccines elicited protective Nab responses, the Nab titres were significantly higher than that in inactivated rabies vaccine group at day 7. Moreover, RABV VLP and VLP/N mRNA vaccines showed superior capacities to elicit potent germinal centre, long-lived plasma cell and memory B cell responses, which linked to high titre and durable Nab responses. In summary, our data demonstrated that RABV VLP and VLP/N mRNA vaccines could be promising candidates against rabies.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Imunidade Celular , Imunidade Humoral , Vacina Antirrábica , Vírus da Raiva , Raiva , Vacinas de Partículas Semelhantes a Vírus , Animais , Vacina Antirrábica/imunologia , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/genética , Raiva/prevenção & controle , Raiva/imunologia , Vírus da Raiva/imunologia , Vírus da Raiva/genética , Camundongos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Feminino , Vacinas de mRNA/imunologia , Camundongos Endogâmicos BALB C , Nucleosídeos/imunologia , Glicoproteínas/imunologia , Glicoproteínas/genética , Humanos , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/genética , Antígenos Virais/imunologia , Antígenos Virais/genética , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , RNA Mensageiro/genética , RNA Mensageiro/imunologiaRESUMO
Rabies is a fatal neurological disorder caused by rabies virus (RABV) infection. Approximately 60,000 patients die from rabies annually, and there are no effective treatments for this disease. Nucleoside analogs are employed as antiviral drugs based on their broad antiviral spectrum, and certain nucleoside analogs have been reported to exhibit anti-RABV activity. The nucleoside analog ß-d-N4-hydroxycytidine (NHC) has antiviral effects against a range of RNA viruses. Molnupiravir (MPV), a prodrug of NHC, is clinically used as an oral antiviral drug for coronavirus infections. Despite its broad-spectrum activity, the antiviral activity of NHC against RABV remains unclear. In this study, we reveal that NHC exhibits comparable in vitro anti-RABV activity as ribavirin and favipiravir (also known as T-705) with a 90% effective concentration of 6 µM in mouse neuroblastoma cells. NHC reduced viral loads in neuronal and nonneuronal cells in a dose-dependent manner. Both laboratory and field RABVs (fixed and street strains, respectively) were susceptible to NHC. However, no increase in survival or reduction in viral titers in the brain was observed in RABV-infected mice treated prophylactically with MPV. These findings highlight the potential and challenges of NHC in the treatment of RABV infection.
Assuntos
Amidas , Antivirais , Citidina , Vírus da Raiva , Raiva , Carga Viral , Animais , Antivirais/farmacologia , Citidina/análogos & derivados , Citidina/farmacologia , Vírus da Raiva/efeitos dos fármacos , Camundongos , Raiva/tratamento farmacológico , Raiva/virologia , Amidas/farmacologia , Carga Viral/efeitos dos fármacos , Pirazinas/farmacologia , Ribavirina/farmacologia , Hidroxilaminas/farmacologia , Linhagem Celular Tumoral , Linhagem CelularRESUMO
Limited data exist on the factors affecting feline rabies vaccination outcomes during primary immunization. This study aimed to assess if specific factors (signalment, vaccination count, vaccine brand, and time since last vaccination) correlated with meeting global antibody titer standards and absolute titers in young cats given monovalent inactivated rabies vaccines. Analyzing a dataset from cats tested before their first annual booster using the FAVN test, logistic and linear regression models were applied. Among 379 cats, 94.2â¯% achieved titers meeting or exceeding the standard threshold (≥0.5 IU/ml). Time since last vaccination proved to be the primary predictor of vaccination success. Cats receiving two vaccinations tended toward higher titers. Age, sex, breed, and vaccine type showed no impact on outcomes. The present study indicates that vaccination failure in young cats is uncommon, and that the time interval from the latest vaccination is the single most important predictor of successful rabies vaccination.
Assuntos
Anticorpos Antivirais , Doenças do Gato , Vacina Antirrábica , Raiva , Vacinação , Animais , Gatos , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/imunologia , Raiva/prevenção & controle , Raiva/veterinária , Doenças do Gato/prevenção & controle , Doenças do Gato/imunologia , Doenças do Gato/virologia , Anticorpos Antivirais/sangue , Vacinação/veterinária , Feminino , Masculino , Vírus da Raiva/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Eficácia de VacinasRESUMO
Despite continuous efforts of veterinary services to control rabies in dogs since 1982, rabies remains a cause of death in Tunisia, with more than five reported human cases in 2022. As little is known on the determinants of transmission of rabies in dogs, better understand which factors contribute to its spatial heterogeneity in Tunisia is critical for developing bespoke mitigation activities. In this context, we developed Bayesian Poisson mixed-effect spatio-temporal model upon all cases of rabid dogs reported in each delegation during the period from 2019 to 2021. The best fitting model highlighted the association between the risk of rabies and the mean average monthly temperature, the density of markets and the density of dogs in delegations. Interestingly, no relationship was found between intensity of vaccination in dogs and the risk of rabies. Our results provided insights into the spatio-temporal dynamics of dog rabies transmission and highlighted specific geographic locations where the risk of infection was high despite correction for associated explanatory variables. Such an improved understanding represent key information to design bespoke, cost-efficient, rabies prevention and control strategies to support veterinary services activities and policymaking.
Assuntos
Doenças do Cão , Raiva , Análise Espaço-Temporal , Raiva/epidemiologia , Raiva/veterinária , Raiva/transmissão , Raiva/prevenção & controle , Cães , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Doenças do Cão/transmissão , Tunísia/epidemiologia , Teorema de Bayes , Vacina Antirrábica/administração & dosagem , Vacinação/veterinária , Vacinação/estatística & dados numéricos , Humanos , Fatores de RiscoRESUMO
Rabies virus (RABV) is the causative agent of rabies, a lethal neurological disease in mammals. RABV strains can be classified into fixed strains (laboratory strains) and street strains (field/clinical strains), which have different properties including cell tropism and neuroinvasiveness. RABV Toyohashi strain is a street strain isolated in Japan from an imported case which had been bitten by rabid dog in the Philippines. In order to facilitate molecular studies of RABV, we established a reverse genetics (RG) system for the study of the Toyohashi strain. The recombinant virus was obtained from a cDNA clone of Toyohashi strain and exhibited similar growth efficiency as the original virus in cultured cell lines. Both the original and recombinant strains showed similar pathogenicity with high neuroinvasiveness in mice, and the infected mice developed a long and inconsistent incubation period, which is characteristic of street strains. We also generated a recombinant Toyohashi strain expressing viral phosphoprotein (P protein) fused with the fluorescent protein mCherry, and tracked the intracellular dynamics of the viral P protein using live-cell imaging. The presented reverse genetics system for Toyohashi strain will be a useful tool to explore the fundamental molecular mechanisms of the replication of RABV street strains.