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Peter J Hudson - One of the best experts on this subject based on the ideXlab platform.
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Ticks need not bite their red grouse hosts to infect them with Louping Ill Virus.
Proceedings of the Royal Society of London. Series B: Biological Sciences, 2004Co-Authors: Lucy Gilbert, Hugh W. Reid, Linda D. Jones, M. Karen Laurenson, E. A. Gould, Peter J HudsonAbstract:For pathogens transmitted by biting vectors, one of the fundamental assumptions is often that vector bites are the sole or main route of host infection. Here, we demonstrate experimentally a transmission route whereby hosts (red grouse, Lagopus lagopus scoticus) became infected with a member of the tick-borne encephalitis Virus complex, Louping Ill Virus, after eating the infected tick vector. Furthermore, we estimated from field observations that this mode of infection could account for 73-98% of all Virus infections in wild red grouse in their first season. This has potential implications for the understanding of other biting vector-borne pathogens where hosts may ingest vectors through foraging or grooming.
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the role of non viraemic transmission on the persistence and dynamics of a tick borne Virus Louping Ill in red grouse lagopus lagopus scoticus and mountain hares lepus timidus
Journal of Mathematical Biology, 2004Co-Authors: Rachel Norman, David Ross, Karen M Laurenson, Peter J HudsonAbstract:There exist many tick borne infections that are of either economic or public health interest. Mathematical models have previously been used to describe the dynamics of these infections. However it has recently come to light that there is an alternative mechanism for the transmission of these diseases that has not been considered in a modelling framework. This is transmission through ticks co-feeding on non-viraemic hosts. This paper extends a simple mathematical model to include this alternative transmission mechanism. The model is used to describe the dynamics of Louping Ill Virus in red grouse (the viraemic host) and hares (the non-viraemic host). However, these results are applicable to many other systems. The model is analysed using joint threshold density curves. It is found that the presence of a non-viraemic host allows the Virus to persist more readily than it would in the presence of a host that simply amplified the tick population. More importantly, if the level of non-viraemic transmission is high enough the Virus can persist in the absence of the viraemic host. This result has important implications for the control of tick borne diseases.
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Identifying disease reservoirs in complex systems: mountain hares as reservoirs of ticks and Louping-Ill Virus, pathogens of red grouse
Journal of Animal Ecology, 2003Co-Authors: M. Karen Laurenson, Lucy Gilbert, Hugh W. Reid, Rachel Norman, Peter J HudsonAbstract:Summary 1 We examined the role of mountain hares in the Louping-Ill Virus/Ixodes ricinus tick system to determine whether hares were reservoirs of these pathogens for red grouse. A field experiment, which involved reducing mountain hare densities was undertaken and changes in tick abundance, Louping-Ill Virus seroprevalence and red grouse densities recorded. 2 Hares were found to be important hosts for all stages of ticks at two study sites and, where sheep were frequently treated with acaricide, hares fed the greatest proportion of adult ticks. Hare densities were reduced at the experimental site between 1993 and 2001 but remained relatively constant at a control site. Both nymph and larvae tick burdens on red grouse chicks declined over this period to very low levels at the treatment site, but not at the control site. The estimated size of the tick population at the treatment site decreased by more than 99% by 1999. 3 Louping-Ill prevalence, as measured by antibody prevalence in shot young red grouse, also declined at the treatment site, lagging behind the tick decline by approximately 2 years. The number of young grouse produced per hen grouse at this treatment site increased in comparison to a second control area. However, no change was found in summer grouse densities and thus we cannot demonstrate parasite-mediated competition. 4 A deterministic SIR-type model describing the dynamics of this pathogen/vector/host system was constructed and used to examine the role of mountain hares in Louping-Ill Virus and tick dynamics. The model predicted a decline in tick numbers and seroprevalence as hare densities reduced. The inclusion of hares as both tick hosts and vector–host–vector transmitters of Louping-Ill Virus gave the best fit to the observed data.
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Harvesting unstable populations: red grouse Lagopus lagopus scoticus (Lath.) in the United Kingdom
Wildlife Biology, 2001Co-Authors: Peter J Hudson, Andrew P DobsonAbstract:The optimal harvesting strategies for unstable populations are explored using first discrete time models and second a continuous time model specifically applied to the destabilising effects of the caecal nematode Trichostrongylus tenuis on the dynamics of red grouse Lagopus lagopus scoticus. In discrete time models, with overcompensation generating either cyclic or chaotic fluctuations in abundance harvesting can act as both a stabilising and a destabilising process. Maximum yields occur at the harvesting rate that coincides with the point where the harvesting stabilises the overcompensation. Optimal harvesting rates increase with the degree of overcompensation although these are more vulnerable to overharvesting. Harvesting in the continuous time model provides similar results, although observed hunting records do not appear to be stabilised by harvesting. Empirical data on the mortality caused by other natural enemies of red grouse, the hen harrier Circus cyaenus and the Louping Ill Virus, show that the...
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role of small mammals in the persistence of Louping Ill Virus field survey and tick co feeding studies
Medical and Veterinary Entomology, 2000Co-Authors: Lucy Gilbert, Peter J Hudson, Ernest A. Gould, Linda D. Jones, H W ReidAbstract:Summary Louping-Ill (LI) is a tick-borne viral disease of red grouse, Lagopus lagopus scoticus Lath. (Tetraonidae: Galliformes), and sheep, Ovis aries L. (Bovidae: Artiodactyla), that causes economic loss to upland farms and sporting estates. Unvaccinated sheep, grouse and mountain hares, Lepus timidus L. (Leporidae: Lagomorpha), are known to transmit LI Virus, whereas red deer, Cervus elaphus L. (Cervidae: Artiodactyla), and rabbits, Oryctolagus cuniculus L. (Leporidae: Lagomorpha), do not. However, the role of small mammals is unknown. Here, we determine the role of small mammals, in particular field voles, Microtus agrestis L. (Muridae: Rodentia), in the persistence of LI Virus on upland farms and sporting estates in Scotland, using field sampling and non-viraemic transmission trials. Small mammals were not abundant on the upland sites studied, few ticks were found per animal and none of the caught animals tested sero-positive to LI Virus. Laboratory trials provided no evidence that small mammals (field voles, bank voles, Clethrionomys glareolus L. (Muridae: Rodentia), and wood mice, Apodemus sylvaticus L. (Muridae: Rodentia), can transmit LI Virus between cofeeding ticks and, in the field, LI Virus was prevalent only in areas with known LI Virus competent hosts (grouse, mountain hares or unvaccinated sheep) and absent elsewhere. In contrast to the case of tick-borne encephalitis (TBE) Virus in Europe, it is concluded that small mammals seem to be relatively unimportant in LI Virus persistence.
Ernest A. Gould - One of the best experts on this subject based on the ideXlab platform.
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molecular basis of a protective neutralizing monoclonal antibody targeting envelope proteins of both tick borne encephalitis Virus and Louping Ill Virus
Journal of Virology, 2019Co-Authors: Xu Yang, Ernest A. Gould, George F. Gao, Ruchao Peng, Lianpan Dai, Po TienAbstract:Tick-borne encephalitis Virus (TBEV) and Louping Ill Virus (LIV) are members of the tick-borne flaviViruses (TBFVs) in the family Flaviviridae which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized. Here, we determined the crystal structures of the LIV envelope (E) protein and report the comparative structural analysis of a TBFV broadly neutralizing murine MAb (MAb 4.2) in complex with either the LIV or TBEV E protein. The structures reveal that MAb 4.2 binds to the lateral ridge of domain III of the E protein (EDIII) of LIV or TBEV, an epitope also reported for other potently neutralizing MAbs against mosquito-borne flaviViruses (MBFVs), but adopts a unique binding orientation. Further structural analysis suggested that MAb 4.2 may neutralize flaviVirus infection by preventing the structural rearrangement required for membrane fusion during Virus entry. These findings extend our understanding of the vulnerability of TBFVs and other flaviViruses (including MBFVs) and provide an avenue for antibody-based TBFV antiviral development. IMPORTANCE Understanding the mechanism of antibody neutralization/protection against a Virus is crucial for antiviral countermeasure development. Tick-borne encephalitis Virus (TBEV) and Louping Ill Virus (LIV) are tick-borne flaviViruses (TBFVs) in the family Flaviviridae. They cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines for both Viruses are available, infection rates are rising due to low vaccination coverage. In this study, we solved the crystal structures of the LIV envelope protein (E) and a broadly neutralizing/protective TBFV MAb, MAb 4.2, in complex with E from either TBEV or LIV. Key structural features shared by TBFV E proteins were analyzed. The structures of E-antibody complexes showed that MAb 4.2 targets the lateral ridge of both the TBEV and LIV E proteins, a vulnerable site in flaviViruses for other potent neutralizing MAbs. Thus, this site represents a promising target for TBFV antiviral development. Further, these structures provide important information for understanding TBFV antigenicity.
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Journal of General Virology (1999), 80, 1189–1198. Printed in Great Britain
2013Co-Authors: Marina N Fleeton, Ernest A. Gould, Brian J. Sheahan, Gregory J. Atkins, Peter Liljestro MAbstract:or NS1 proteins of Louping Ill Virus protect mice from lethal challeng
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detection of Louping Ill Virus in clinical specimens from mammals and birds using taqman rt pcr
Journal of Virological Methods, 2006Co-Authors: L. Marriott, Ernest A. Gould, K. Willoughby, F Chianini, M P Dagleish, Sandra Scholes, A C Robinson, P F NettletonAbstract:The identification of Louping Ill Virus (LIV) in clinical specimens has been routinely achieved by Virus isolation using susceptible pig kidney cells and subsequent serological analysis. While this method is sensitive and detects infectious Virus, it is relatively labour intensive and time-consuming. In view of the veterinary and potential medical importance of LIV, a rapid and precise detection method for routine use that employs the TaqMan reverse transcription polymerase chain reaction (RT-PCR) has been developed to detect LIV RNA extracted from field samples. The TaqMan assay was evaluated against Virus isolation using 22 cell culture grown LIV isolates, which had previously been partially characterised by sequencing, and material from 63 suspect field cases. Histopathological and/or serological reports were available for 39 of the suspect cases, providing additional diagnostic information to evaluate the results obtained from the TaqMan RT-PCR assay. The TaqMan assay was as sensitive as the cell culture infectious Virus assay currently used and had the advantage that it was able to detect LIV in clinical specimens from which infectious Virus could not be isolated possibly due to the presence of high levels of LIV antibody.
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potential arboVirus emergence and implications for the united kingdom
Emerging Infectious Diseases, 2006Co-Authors: Ernest A. Gould, Stephen Higgs, Alan Buckley, T.s. GritsunAbstract:ArboViruses have evolved a number of strategies to survive environmental challenges. This review examines the factors that may determine arboVirus emergence, provides examples of arboViruses that have emerged into new habitats, reviews the arboVirus situation in western Europe in detail, discusses potential arthropod vectors, and attempts to predict the risk for arboVirus emergence in the United Kingdom. We conclude that climate change is probably the most important requirement for the emergence of arthropodborne diseases such as dengue fever, yellow fever, Rift Valley fever, Japanese encephalitis, Crimean-Congo hemorrhagic fever, bluetongue, and African horse sickness in the United Kingdom. While other arboViruses, such as West Nile Virus, Sindbis Virus, Tahyna Virus, and Louping Ill Virus, apparently circulate in the United Kingdom, they do not appear to present an imminent threat to humans or animals.
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Tick-borne Virus diseases of human interest in Europe.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2004Co-Authors: Rémi N. Charrel, T.s. Gritsun, Ernest A. Gould, J.c. Clegg, Vincent Deubel, T.v. Frolova, Franz X. Heinz, Milan LabudaAbstract:Several human diseases in Europe are caused by Viruses transmitted by tick bite. These Viruses belong to the genus FlaviVirus, and include tick-borne encephalitis Virus, Omsk haemorrhagic fever Virus, Louping Ill Virus, Powassan Virus, NairoVirus (Crimean-Congo haemorrhagic fever Virus) and ColtiVirus (Eyach Virus). All of these Viruses cause more or less severe neurological diseases, and some are also responsible for haemorrhagic fever. The epidemiology, clinical picture and methods for diagnosis are detailed in this review. Most of these viral pathogens are classified as Biosafety Level 3 or 4 agents, and therefore some of them have been classified in Categories A–C of potential bioterrorism agents by the Centers for Disease Control and Prevention. Their ability to cause severe disease in man means that these Viruses, as well as any clinical samples suspected of containing them, must be handled with specific and stringent precautions.
Lucy Gilbert - One of the best experts on this subject based on the ideXlab platform.
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identifying environmental risk factors for Louping Ill Virus seroprevalence in sheep and the potential to inform wildlife management policy
Frontiers in Veterinary Science, 2020Co-Authors: Lucy Gilbert, Franz Brulisauer, Kim Willoughby, Chris CousensAbstract:Identifying the risk factors for disease is crucial for developing policy and strategies for controlling exposure to pathogens. However, this is often challenging, especially in complex disease systems, such as vector-borne diseases with multiple hosts and other environmental drivers. Here we combine seroprevalence data with GIS-based environmental variables to identify the environmental risk factors associated with an endemic tick-borne pathogen - Louping Ill Virus –in sheep in Scotland. Higher seroprevalences were associated with (i) upland/moorland habitats, in accordance with what we predicted from the habitat preferences of alternative LIV transmission hosts (such as red grouse), (ii) areas of higher deer density, which supports predictions from previous theoretical models, since deer are the key Ixodes ricinus tick reproduction host in this system, and (iii) a warmer climate, concurring with our current knowledge of how temperature affects tick activity and development rates. The implications for policy include adopting increased disease management and awareness in high risk habitats and in the presence of alternative LIV hosts (e.g. grouse) and tick hosts (especially deer). These results can also inform deer management policy, especially where there may be conflict between contrasting upland management objectives, for example, revenue from deer hunting versus sheep farmers.
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Louping Ill Virus in the UK: a review of the hosts, transmission and ecological consequences of control
Experimental and Applied Acarology, 2016Co-Authors: Lucy GilbertAbstract:Louping Ill Virus (LIV) is a tick-borne flaviVirus that is part of the tick-borne encephalitis complex of Viruses (TBEV) and has economic and welfare importance by causing Illness and death in livestock, especially sheep, Ovies aries , and red grouse, Lagopus lagopus scoticus , an economically valuable gamebird. Unlike Western TBEV which is found primarily in woodlands and is reservoired by small rodents, LIV is not generally transmitted by small rodents but instead by sheep, red grouse and mountain hares and, therefore, is associated with upland heather moorland and rough grazing land. Red grouse are a particularly interesting transmission host because they may acquire most of their LIV infections through eating ticks rather than being bitten by ticks. Furthermore, the main incentive for the application of LIV control methods is not to protect sheep, but to protect red grouse, which is an economically important gamebird. The widespread intensive culling of mountain hares which has been adopted in several areas of Scotland to try to control ticks and LIV has become an important issue in Scotland in recent years. This review outlines the reservoir hosts and transmission cycles of LIV in the UK, then describes the various control methods that have been tried or modelled, with far-reaching implications for conservation and public opinion.
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a model to test how ticks and Louping Ill Virus can be controlled by treating red grouse with acaricide
Medical and Veterinary Entomology, 2013Co-Authors: Rosalyn Porter, Rachel Norman, Lucy GilbertAbstract:Ticks are the most important vectors of disease-causing pathogens in Europe. In the U.K., Ixodes ricinus L. (Ixodida: Ixodidae) transmits Louping Ill Virus (LIV; Flaviviridae), which kIlls livestock and red grouse, Lagopus lagopus scoticus Lath. (Galliformes: Phasianidae), a valuable game bird. Tick burdens on grouse have been increasing. One novel method to reduce ticks and LIV in grouse may be acaricide treatment. Here, we use a mathematical model parameterized with empirical data to investigate how the acaricide treatment of grouse might theoretically control ticks and LIV in grouse. Assuming a situation in which ticks and LIV impact on the grouse population, the model predicts that grouse density wIll depend on deer density because deer maintain the tick population. In low deer densities, no acaricide treatment is predicted to be necessary because abundances of grouse wIll be high. However, at higher deer densities, the model predicts that grouse densities wIll increase only if high numbers of grouse are treated, and the efficacy of acaricide is high and lasts 20 weeks. The qualitative model predictions may help to guide decisions on whether to treat grouse or cull deer depending on deer densities and how many grouse can be treated. The model is discussed in terms of practical management implications.
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The effect of landscape heterogeneity and host movement on a tick-borne pathogen
Theoretical Ecology, 2011Co-Authors: Edward O. Jones, Steven D. Webb, Francisco J. Ruiz-fons, Steven Albon, Lucy GilbertAbstract:Landscape heterogeneity can be instrumental in determining local disease risk, pathogen persistence and spread. This is because different landscape features such as habitat type determine the abundance and spatial distributions of hosts and pathogen vectors. Therefore, disease prevalence and distribution are intrinsically linked to the hosts and vectors that utilise the different habitats. Here, we develop a simplified reaction diffusion model of the Louping-Ill Virus and red grouse ( Lagopus lagopus scoticus ) system to investigate the occurrence of a tick-borne pathogen and the effect of host movement and landscape structure. Ticks ( Ixodes ricinus ), the Virus-vector, are dispersed by a virally incompetent tick host, red deer ( Cervus elephus ), between different habitats, whilst the Virus infects only red grouse. We investigated how deer movement between different habitats (forest and moorland) affected tick distribution and hence prevalence of infected ticks and grouse and hence, the effect of habitat size ratio and fragmentation on infection. When habitat type has a role in the survival of the pathogen vector, we demonstrated that habitat fragmentation can have a considerable effect on infection. These results highlight the importance of landscape heterogeneity and the proximity and size of adjacent habitats when predicting disease risk in a particular location. In addition, this model could be useful for other pathogen systems with generalist vectors and may inform policy on possible disease management strategies that incorporate host movements.
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Culling wildlife hosts to control disease: mountain hares, red grouse and Louping Ill Virus
Journal of Applied Ecology, 2010Co-Authors: Annabel Harrison, Lucy Gilbert, Daniel T. Haydon, Scott Newey, Simon J. ThirgoodAbstract:Summary 1. Culling wildlife hosts is often implemented as a management technique to control pathogen transmission from wildlife to domestic or other economically important animals. However, culling may have unexpected consequences, can be expensive and may have wider implications for biodiversity and ecosystem functioning. 2. We assess the evidence that culling mountain hares Lepus timidus is an effective and practical way to control Louping Ill Virus in red grouse Lagopus lagopus scoticus. 3. Evidence from the available literature is limited, restricting our ability to reliably assess the effectiveness of culling mountain hares to control ticks, Louping Ill Virus, or increase red grouse densities. Furthermore, the information required to assess the cost-benefit of this management strategy is lacking. The population response of mountain hares to culling is not well understood and the possible effects on their conservation status and the upland ecosystem remain unexplored. 4. We conclude that there is no compelling evidence base to suggest culling mountain hares might increase red grouse densities. 5. Synthesis and applications. Widespread culling of wildlife is not necessarily effective in reducing disease or improving economic returns. The use of wildlife culls for disease control should be proposed only when: (i) the pathogen transmission cycle is fully understood with all host-vector interactions considered; (ii) the response of wildlife populations to culling is known; and (iii) cost-benefit analysis shows that increased revenue from reduced disease prevalence exceeds the cost of culling.
G J Atkins - One of the best experts on this subject based on the ideXlab platform.
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self replicative rna vaccines elicit protection against influenza a Virus respiratory syncytial Virus and a tickborne encephalitis Virus
The Journal of Infectious Diseases, 2001Co-Authors: Marina N Fleeton, G J Atkins, Margaret Chen, Peter Berglund, Gary Rhodes, Suezanne E Parker, Marie Murphy, Peter LiljestromAbstract:In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha Virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest Virus RNA-encoding envelope proteins from one of 3 Viruses: influenza A Virus, a tickborne flaviVirus (Louping Ill Virus), or respiratory syncytial Virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model Virus diseases.
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recombinant semliki forest Virus particles expressing Louping Ill Virus antigens induce a better protective response than plasmid based dna vaccines or an inactivated whole particle vaccine
Journal of General Virology, 2000Co-Authors: Marina N Fleeton, Peter Liljestrom, B J Sheahan, G J AtkinsAbstract:Louping Ill Virus (LIV) infection of mice was used as a model to evaluate the protective efficacy of Semliki Forest Virus (SFV)-based vaccines in comparison to a standard DNA vaccine and a commercial chemically inactivated vaccine. The recombinant SFV-based vaccines consisted of suicidal particles and a naked layered DNA/RNA construct. The nucleic acid vaccines expressed the spike precursor prME and the nonstructural protein 1 (NS1) antigens of LIV. Three LIV strains of graded virulence for mice were used for challenge. One of these was a naturally occurring antibody escape variant. All vaccines tested induced humoral immunity but gave varying levels of protection against lethal challenge. Only recombinant SFV particles administered twice gave full protection against neuronal degeneration and encephalitis induced by two of the three challenge strains, and partial protection against the highly virulent strain, whereas the other vaccines tested gave lower levels of partial protection.
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recombinant semliki forest Virus particles encoding the prme or ns1 proteins of Louping Ill Virus protect mice from lethal challenge
Journal of General Virology, 1999Co-Authors: Marina N Fleeton, E. A. Gould, B J Sheahan, G J AtkinsAbstract:Recombinant Semliki Forest Virus (rSFV) vaccines encoding Louping Ill Virus (LIV) genes prME and NS1 were examined. Cells transfected with rSFV-prME RNA showed correct processing of the precursor prME and the release into the medium of M and E proteins in particulate form, whilst rSFV-NS1-transfected cells secreted glycosylated, heat-labile NS1 dimers. Mice immunized with rSFV particles produced antibodies against prME and NS1 that were mainly of the IgG2a subtype, indicating that a T-helper 1 immune response was induced. Immunization with prME- or NS1-encoding particles induced T-cell proliferation. Mice vaccinated intraperitoneally (i.p.) with rSFV-prME and/or rSFV-NS1 were significantly protected from lethal i.p. challenge by two strains of LIV, the virulent LI/31 strain, from which the commercial LIV vaccine is derived, and the less-virulent LI/I antibody-escape variant. Intranasal (i.n.) vaccination was protective for rSFV-prME only against LI/31 challenge and not against challenge with LI/I. Immunization with rSFV-NS1 was protective against i.p. and i.n. challenge with both Virus strains when given i.p., but was not protective when given i.n. For unvaccinated mice infected with LIV, all animals showing clinical signs had severe degenerative and inflammatory lesions in the central nervous system. None of the rSFV-vaccinated mice that survived challenge showed central nervous system pathology, with the exception of mild leptomeningitis in a minority of LI/31-infected mice. This suggests that protection following immunization with rSFV must occur at early stages of LIV infection.
Marina N Fleeton - One of the best experts on this subject based on the ideXlab platform.
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Journal of General Virology (1999), 80, 1189–1198. Printed in Great Britain
2013Co-Authors: Marina N Fleeton, Ernest A. Gould, Brian J. Sheahan, Gregory J. Atkins, Peter Liljestro MAbstract:or NS1 proteins of Louping Ill Virus protect mice from lethal challeng
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self replicative rna vaccines elicit protection against influenza a Virus respiratory syncytial Virus and a tickborne encephalitis Virus
The Journal of Infectious Diseases, 2001Co-Authors: Marina N Fleeton, G J Atkins, Margaret Chen, Peter Berglund, Gary Rhodes, Suezanne E Parker, Marie Murphy, Peter LiljestromAbstract:In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha Virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest Virus RNA-encoding envelope proteins from one of 3 Viruses: influenza A Virus, a tickborne flaviVirus (Louping Ill Virus), or respiratory syncytial Virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model Virus diseases.
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recombinant semliki forest Virus particles expressing Louping Ill Virus antigens induce a better protective response than plasmid based dna vaccines or an inactivated whole particle vaccine
Journal of General Virology, 2000Co-Authors: Marina N Fleeton, Peter Liljestrom, B J Sheahan, G J AtkinsAbstract:Louping Ill Virus (LIV) infection of mice was used as a model to evaluate the protective efficacy of Semliki Forest Virus (SFV)-based vaccines in comparison to a standard DNA vaccine and a commercial chemically inactivated vaccine. The recombinant SFV-based vaccines consisted of suicidal particles and a naked layered DNA/RNA construct. The nucleic acid vaccines expressed the spike precursor prME and the nonstructural protein 1 (NS1) antigens of LIV. Three LIV strains of graded virulence for mice were used for challenge. One of these was a naturally occurring antibody escape variant. All vaccines tested induced humoral immunity but gave varying levels of protection against lethal challenge. Only recombinant SFV particles administered twice gave full protection against neuronal degeneration and encephalitis induced by two of the three challenge strains, and partial protection against the highly virulent strain, whereas the other vaccines tested gave lower levels of partial protection.
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recombinant semliki forest Virus particles encoding the prme or ns1 proteins of Louping Ill Virus protect mice from lethal challenge
Journal of General Virology, 1999Co-Authors: Marina N Fleeton, E. A. Gould, B J Sheahan, G J AtkinsAbstract:Recombinant Semliki Forest Virus (rSFV) vaccines encoding Louping Ill Virus (LIV) genes prME and NS1 were examined. Cells transfected with rSFV-prME RNA showed correct processing of the precursor prME and the release into the medium of M and E proteins in particulate form, whilst rSFV-NS1-transfected cells secreted glycosylated, heat-labile NS1 dimers. Mice immunized with rSFV particles produced antibodies against prME and NS1 that were mainly of the IgG2a subtype, indicating that a T-helper 1 immune response was induced. Immunization with prME- or NS1-encoding particles induced T-cell proliferation. Mice vaccinated intraperitoneally (i.p.) with rSFV-prME and/or rSFV-NS1 were significantly protected from lethal i.p. challenge by two strains of LIV, the virulent LI/31 strain, from which the commercial LIV vaccine is derived, and the less-virulent LI/I antibody-escape variant. Intranasal (i.n.) vaccination was protective for rSFV-prME only against LI/31 challenge and not against challenge with LI/I. Immunization with rSFV-NS1 was protective against i.p. and i.n. challenge with both Virus strains when given i.p., but was not protective when given i.n. For unvaccinated mice infected with LIV, all animals showing clinical signs had severe degenerative and inflammatory lesions in the central nervous system. None of the rSFV-vaccinated mice that survived challenge showed central nervous system pathology, with the exception of mild leptomeningitis in a minority of LI/31-infected mice. This suggests that protection following immunization with rSFV must occur at early stages of LIV infection.
