Experimental infection of Foxes with European bat Lyssaviruses type-1 and 2

<p>Abstract</p> <p>Background</p> <p>Since 1954, there have been in excess of 800 cases of rabies as a result of European Bat <it>Lyssaviruses </it>types 1 and 2 (EBLV-1, EBLV-2) infection, mainly in Serotine and Myotis bats respectively. These viruses have rarely been reported to infect humans and terrestrial mammals, as the only exceptions are sheep in Denmark, a stone marten in Germany and a cat in France. The purpose of this study was to investigate the susceptibility of foxes to EBLVs using silver foxes (<it>Vulpes vulpes</it>) as a model.</p> <p>Results</p> <p>Our experimental studies have shown that the susceptibility of foxes to EBLVs is low by the intramuscular (IM) route, however, animals were sensitive to intracranial (IC) inoculation. Mortality was 100% for both EBLV-1 (~4.5 logs) and EBLV-2 (~3.0 logs) delivered by the IC route. Virus dissemination and inflammatory infiltrate in the brain were demonstrated but virus specific neutralising antibody (VNA) was limited (log(ED₅₀) = 0.24–2.23 and 0.95–2.39 respectively for specific EBLV-1 and EBLV-2). Foxes were also susceptible, at a low level, to peripheral (IM) infection (~3.0 logs) with EBLV-1 but not EBLV-2. Three out of 21 (14.3%) foxes developed clinical signs between 14 and 24 days post-EBLV-1 infection. None of the animals given EBLV-2 developed clinical disease.</p> <p>Conclusion</p> <p>These data suggest that the chance of a EBLV spill-over from bat to fox is low, but with a greater probability for EBLV-1 than for EBLV-2 and that foxes seem to be able to clear the virus before it reaches the brain and cause a lethal infection.</p

Serologic Surveillance for SARS-CoV-2 Infection among Wild Rodents, Europe

Publisher Copyright: © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved.Peer reviewe

OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) protein of SARS-CoV-2 genetically fused to oligoDOM®, a self-assembling domain which improves antigen immunogenicity. OVX033 including N as an antigenic target is proposed as new vaccine candidate providing broad-spectrum protection against sarbecoviruses. OVX033 demonstrated its ability to trigger cross-reactive T cell responses and cross-protection against three variants of SARS-CoV-2 (B.1 Europe, Delta B.1.617.2, and Omicron B.1.1.529) in a hamster challenge model, as evidenced by lower weight loss, lower lung viral loads, and reduced lung histopathological lesions

Input of immunity detection tools adapted to the epidemiological context for control and surveillance of animal rabies

La rage est une zoonose mortelle, susceptible d’atteindre autant les mammifères sauvages et domestiques que l’Homme. Elle est à l’origine d’environ 70 000 décès humain déclarés par an, majoritairement des enfants dans les pays en développement. Le chien, réservoir majeur de l’espèce RABV, est à l’origine de 98-99% de ces décès. Quatorze espèces de Lyssavirus, circulant majoritairement chez les chiroptères sont actuellement reconnues. La vaccination, associée à des mesures sanitaires, reste le meilleur outil de prévention et de maîtrise de la maladie. A l’heure actuelle, seule la sérologie permet de contrôler l’efficacité de la vaccination antirabique, le développement des anticorps neutralisants étant le premier témoin d’une immunité protectrice. Les travaux s’appuyant sur la séroneutralisation virale, et notamment ceux auxquels j’ai participé, ont mis en évidence l’influence de différents facteurs dont certains ont conduit à préconiser des modifications de protocoles vaccinaux. Ils ont également permis d’assurer le suivi de l’efficacité de la vaccination individuelle ou de groupe sur le terrain et de contribuer à son amélioration. Les tests de séroneutralisation sont également utilisés dans le cadre de l’épidémiosurveillance de populations animales non vaccinées. La mise en œuvre de ces tests chez les chiroptères en France, après leur adaptation au Lyssavirus d’intérêt que j’ai menée à bien, a permis d’obtenir des informations sur la circulation des espèces virales EBLV-1 et EBLV-2, sur une base uniquement sérologique pour ce dernier. D’autre part, elle a permis de mettre en évidence au sein d’une même colonie des phénomènes de transition sérologique au cours du temps, dont l’étude mériterait d’être approfondie. Les tests de séroneutralisation sont cependant difficilement transférables aux pays où la rage est très présente, du fait de ressources limitées. Mes travaux, proposant l’utilisation d’un test ELISA comme méthode alternative, ont contribué à remettre en cause le dogme du recours nécessaire à la séroneutralisation. Ce test, couplé à un système de collecte d’échantillons sanguins adapté au terrain, devrait améliorer le suivi de l’efficacité des campagnes de vaccination de la faune sauvage comme des animaux domestiques, y compris dans les pays d’enzootie où la qualité des prélèvements de sang ne peut être assurée. Ainsi, les outils d’évaluation de la réponse immunitaire humorale sont des outils très précieux au service de la lutte et de la surveillance de la rage animale dans le monde. Mes travaux, complémentaires à ceux réalisés par d’autres équipes, ont contribué à rendre envisageable l’objectif prioritaire des organisations internationales : l’éradication de la rage canine dans le monde à l’horizon 2030. Il est cependant nécessaire de les poursuivre pour améliorer les outils disponibles et d’en proposer de plus adaptés, afin d’atteindre l’ensemble des objectifs d’éradication, de la rage canine comme de la rage selvatiqueRabies is a deadly zoonosis that can affect wild and domestic mammals as much as humans. About 70,000 human deaths are reported each year, mostly in children from developing countries. Dogs, which are the major reservoir and source of the RABV species, account for 98-99% of these deaths. Currently, fourteen species of Lyssavirus, mainly circulating in chiroptera, are officially recognized. Vaccination, combined with sanitary measures, remains the best tool for preventing and controlling the disease. To date, only serology has allowed to control the effectiveness of rabies vaccination, as the production of neutralizing antibodies is the first evidence of protective immunity. Studies based on viral seroneutralisation, including my own studies, have highlighted the influence of various factors. Some of them have led to recommend modifications of vaccine protocols. They also contributed to monitor the effectiveness of individual or group vaccination field programmes and to improve these programmes. Seroneutralisation tests are also used in the context of the epidemiological surveillance of unvaccinated animal populations. I first successfully adapted these tests to lyssaviruses of interest in France. In a second step, their implementation in chiropters in France provided information on the circulation of EBLV-1 and EBLV-2 species, (only on a serological basis for the latter). This survey also allowed to highlight, within a specific colony, a phenomenon of serological transition over time, which should deserve to be studied further. However, seroneutralisation tests are difficult to be implemented in countries where rabies is very prevalent, mainly because of limited resources. My work, which recommends the use of an ELISA test as an alternative method, contributed to questioning the dogma of the necessary use of seroneutralisation tests. This test, coupled with a blood sampling system adapted to the field, should improve the monitoring of the effectiveness of vaccination campaigns for both wildlife and domestic animals, including in enzootic countries, where the quality of the blood samples cannot be guaranteed. Humoral immune response assessment tools are very valuable tools for the control and surveillance of animal rabies all around the world. My work, complementary to those carried out by other teams, has helped to make the priority objective of international organizations possible, i.e. the eradication of canine rabies in the world by 2030. However, further works are needed to improve the available tools and to propose more adapted ones, in order to achieve all the goals of eradication, for both canine and sylvatic rabie

Comparison of antibody titres between intradermal and intramuscular rabies vaccination using inactivated vaccine in cattle in Bhutan.

In developing countries, the cost of vaccination limits the use of prophylactic rabies vaccination, especially in cattle. Intradermal vaccination delivers antigen directly to an area with higher number of antigen-presenting cells. Therefore, it could produce equivalent or higher antibody titres than conventional intramuscular vaccination even when a lower dose is given. This study aimed to compare the antibody response in cattle vaccinated intramuscularly with 1mL of inactivated rabies vaccine (Raksharab, Indian Immunologicals) against intradermally vaccinated cattle with 0.2mL of the same vaccine. The study was conducted in Haa province of Bhutan where rabies is not endemic. One hundred cattle from 27 farms were selected for the study. Virus neutralising antibody (VNA) response was measured using the fluorescent antibody virus neutralisation test on the day of vaccination (day 0) and 14, 30, 60 and 90 days later. Overall, 71% of intradermally vaccinated cattle and 89% of the intramuscularly vaccinated cattle produced an adequate response (≥0.5IU/mL). On days 14 and 30 post vaccination fewer cattle (P 0.6 IU/mL. Although low dose intradermal vaccination did produce a detectable antibody response, it was inferior to intramuscular vaccination. Thus, although intradermal vaccination has the potential to reduce the cost of vaccination by reducing the dose required, this study showed that a single dose of 0.2 mL intradermally was inferior to an intramuscular dose of 1 mL. Further research evaluating dose and dose regimen is needed before intradermal vaccination using the Raksharab rabies vaccine can be recommended in cattle

Bat rabies surveillance in France: first report of unusual mortality among serotine bats

Abstract Background Rabies is a fatal viral encephalitic disease that is caused by lyssaviruses which can affect all mammals, including human and bats. In Europe, bat rabies cases are attributed to five different lyssavirus species, the majority of rabid bats being attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). In France, rabies in bats is under surveillance since 1989, with 77 positive cases reported between 1989 and 2016. Case presentation In the frame of the bat rabies surveillance, an unusual mortality of serotine bats was reported in 2009 in a village in North-East France. Six juvenile bats from an E. serotinus maternity colony counting ~200 individuals were found to be infected with EBLV-1. The active surveillance of the colony by capture sessions of bats from July to September 2009 showed a high detection rate of neutralising EBLV-1 antibodies (≈ 50%) in the colony. Moreover, one out of 111 animals tested was found to shed viable virus in saliva, while lyssavirus RNA was detected by RT-PCR for five individuals. Conclusion This study demonstrated that the lyssavirus infection in the serotine maternity colony was followed by a high rate of bat rabies immunity after circulation of the virus in the colony. The ratio of seropositive bats is probably indicative of an efficient virus transmission coupled to a rapid circulation of EBLV-1 in the colony

Filter Papers to Collect Blood Samples from Dogs: An Easier Way to Monitor the Mass Vaccination Campaigns against Rabies?

Rabies is a deadly viral disease present mainly in low-income countries of Africa and Asia. Dogs are the main reservoir and the source of human deaths. Mass vaccination campaigns of dogs are pivotal to achieve rabies elimination. The monitoring of the immune response of the dog population is necessary to evaluate the effectiveness of these campaigns, taking into account field conditions. This study explores the feasibility and the performance of a new tool using filter papers (FPs) to collect blood samples associated with an Enzyme-Linked ImmunoSorbent Assay (ELISA) titration of rabies antibodies in dogs. A total of 216 eluates from FP samples were collected from 111 dogs kept in experimental facilities in France and 29 dogs from the field in Tunisia. Sera were also analyzed using both the Fluorescence Antibody Virus Neutralization test (FAVNt) and ELISA. A high specificity (98.0%) was obtained by testing FP blood eluates from 51 unvaccinated dogs, with the results compared with those of FAVNt and ELISA on serum samples. The coefficients of concordance between FP eluates and tested sera were 88.9% for FAVNt and 88.0% for ELISA. Blood filter papers coupled with the titration of rabies antibodies by ELISA provide a reliable, simple, and effective solution to overcome the issues of the logistics and transport of samples, especially in low-income countries

Proficiency test for rabies serology: A design complying with international standards for a reliable assessment of participating laboratories

International audienceBACKGROUND: Domestic carnivores can introduce rabies into disease-free countries or areas if they are incubating the disease and transported during the pre-symptomatic period. For pets moved into the European Union, the European Commission decided to establish a system of community approval of laboratories willing to carry out the rabies serological controls to guarantee an effective control system. As the specific institute to coordinate the approval of the laboratories, designated by the European Commission in 2000, our laboratory organizes annual proficiency tests (PT) for laboratories already agreed or willing to be agreed to perform rabies serological controls (by detecting rabies virus neutralizing antibodies only) in the frame of international trade.METHODOLOGY/PRINCIPAL FINDINGS: The assessment criteria of this PT rely on the analysis of the specificity and the intra-laboratory consistency. The approach used to evaluate the degree of laboratory consistency is based on the use of compiled data obtained from previous PT campaigns, and is measured by the quality of a regression model. By using historical data for calculating assigned values and associated standard deviations, instead of values obtained from only one campaign, they became robust without any additional statistical treatment. In the present paper, more than 800 historical values were compiled for each of the regression parameters.CONCLUSIONS/SIGNIFICANCE: Since the beginning of these PT schemes in 1999, the overall percentage of failing laboratories remained stable over the years (4.1%) while the number of participants increased to 79 in 2018. This highlighted the robustness and the consistency of the statistical analyses used to assess the laboratory's performance over the years. The improvements carried out and the consistency of our statistical analyses have resulted in the compliance of the rabies serology PT with the ISO/IEC 17043 and ISO 13528:2015 International Standards

A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer?

Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease’s vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976–2015) thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005–2015). Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a “One Health” approach. Dog population ecology parameters’ study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating legislation by inclusion of responsible dog ownership and law enforcement are crucial. Over the last century, Morocco registered a slow decreasing tendency in the number of animal and human rabies cases. Urgent strategy need to be implemented because rabies elimination is an achievable goal in Morocco

Molecular and serological survey of lyssaviruses in Croatian bat populations

Abstract Background Rabies is the only known zoonotic disease of bat origin in Europe. The disease is caused by species belonging to the genus Lyssavirus. Five Lyssavirus species, i.e., European bat lyssavirus (EBLV)-1, EBLV-2, Bokeloh bat lyssavirus, Lleida bat lyssavirus, and West Caucasian bat virus, have been identified in European bats. More recently, a proposed sixth species, Kotalahti bat lyssavirus, was detected. Thus, in this study, active surveillance was initiated in order to obtain insights into the prevalence of lyssaviruses in Croatian bat populations and to improve our understanding of the public health threat of infected bats. Results In total, 455 bats were caught throughout Continental and Mediterranean Croatia. Antibodies were found in 20 of 350 bats (5.71%, 95% confidence interval 3.73–8.66). The majority of seropositive bats were found in Trbušnjak cave (Continental Croatia, Eastern part), and most seropositive bats belonged to Myotis myotis (13/20). All oropharyngeal swabs were negative for the presence of Lyssavirus. Conclusions The presence of lyssaviruses in bat populations was confirmed for the first time in Croatia and Southeastern Europe. The results of this study suggest the need for further comprehensive analyses of lyssaviruses in bats in this part of Europe