Biology subjects

Darpel, K.

Publications and source records attributed to Darpel, K..

3 recordsLinked to original sources

bioRxiv2025

Immunization with a novel RNA replicon vaccine confers long-lasting protection against H5N1 avian influenza virus in 24 bird species

Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 (clade 2.3.4.4b) have spread worldwide and caused the death of hundreds of millions of wild birds and domestic poultry. Moreover, spill over of H5N1 HPAIV from infected birds to more than 50 different mammalian species including humans has been recorded. While, licensed vaccines for protection of avian or mammalian species are not yet available, a few candidate vaccines are being trialled. Here, we report on the experimental vaccination of chickens and captive wild birds using a propagation-defective vesicular stomatitis virus (VSV), in which the essential envelope glycoprotein (G) protein gene was replaced by a modified hemagglutinin gene derived from a clade 2.3.4.4b H5N1 isolated in 2022 in the animal park of Bern, Switzerland. VSV{Delta}G(H5mb) was produced on helper cells providing the VSV G protein in trans. Specific pathogen-free (SPF) chickens that were immunized twice via the intramuscular route with adjuvant-free VSV{Delta}G(H5mb) replicon particles induced high levels of virus-neutralizing serum antibodies and were fully protected against lethal infection by H5N1 HPAIV (clade 2.3.4.4b). Notably, immunized animals did not shed challenge virus from the respiratory or gastrointestinal tract, suggesting that herd immunity can be achieved. The same vaccine was used to immunize a total of 317 captive wild birds at Bern Animal Park and Zoo Basel, representing 24 different species. No vaccine-associated side effects were observed. Birds without previous contact to H5Nx viruses produced high to very high H5-specific neutralizing antibody titers following the second immunization, while birds showing H5-specific antibodies prior to vaccination, already developed high neutralising antibody titers after a single immunization. One year after vaccination, most animals still showed significant neutralizing antibody titers, indicating that VSV{Delta}G(H5mb) is able to induce a long-lasting protective immune response. Our results indicate that VSV{Delta}G(H5mb) is an extraordinary safe and highly efficacious vaccine to stop H5N1 replication in various avian species.

microbiology↗

bioRxiv2023

The mechanical arthropod vector Stomoxys calcitrans influences the outcome of lumpy skin disease virus infection in cattle

The poxvirus lumpy skin disease virus (LSDV) is the etiological agent of lumpy skin disease (LSD), a severe disease of cattle and water buffalo that is characterised by numerous necrotic cutaneous nodules. LSD is a rapidly emerging disease, spreading into and across the Middle East, eastern Europe, and Asia in the past decade. The disease causes substantial production and economic losses in rural communities and affected regions. LSDV is mechanically transmitted by haematophagous arthropods including stable flies (Stomoxys calcitrans), however our understanding of this mechanical transmission method is sparse. A secreted saliva collection methodology using a modified artificial membrane feeding system was optimised for S. calcitrans and used to collect and characterise secreted S. calcitrans saliva. Saliva was mixed with LSDV and shown not to affect virus growth in primary bovine fibroblasts. S. calcitrans saliva or spot-feeding by S. calcitrans was then incorporated into a bovine in vivo experimental model of LSD to determine if either influenced disease pathogenesis. S. calcitrans saliva resulted in fewer animals developing disease, however this difference was not statistically significant. Spot-feeding with S. calcitrans prior to inoculation did not alter the number of animals that developed disease or the overall severity of disease however disease progression was accelerated as demonstrated by the appearance of cutaneous nodules, detection of viral DNA in the blood stream, and production of neutralising antibodies. This shows that S. calcitrans influence disease kinetics through co-incident bite trauma and/or saliva deposition. This increases our understanding of LSDV pathogenesis and highlights the overlooked importance of mechanical vectors in pathogen transmission. Author summaryInsect vectors are important conduits for the transmission of pathogens that cause diseases such as Zika, dengue, malaria, and lumpy skin disease. Biological vector-borne transmission incorporates a replication phase for the pathogen in the insect, whereas no replication occurs in the vector during mechanical transmission. When the insect bites the host it inoculates a pathogen whilst also delivering arthropod-derived factors such as saliva components and causing tissue trauma through biting and probing. Arthropod saliva and/or bite trauma have been shown to enhance the speed and severity of disease following inoculation with a range of biologically transmitted viruses. This study examined if this was true also for the mechanically transmitted pathogen lumpy skin disease virus (LSDV). LSDV is a neglected pathogen that causes severe systemic disease in cattle and is transmitted mechanically by the stable fly Stomoxys calcitrans. Using an experimental bovine model of LSD, we found that disease occurred more rapidly when virus was delivered in association with the bites of uninfected flies. This work has increased our knowledge of lumpy skin disease virus transmission, and the discovery that disease outcome can be impacted by previously overlooked mechanical insect vectors should prompt further investigation into this mechanism of transmission.

microbiology↗

bioRxiv2018

Evidence of reduced viremia, pathogenicity and vector competence in a re-emerging European strain of bluetongue virus serotype 8 in sheep

The outbreak of bluetongue virus (BTV) serotype 8 (BTV-8) during 2006-2009 in Europe was the most costly epidemic of the virus in recorded history. In 2015, a BTV-8 strain re-emerged in France which has continued to circulate since then. To examine anecdotal reports of reduced pathogenicity and transmission efficiency, we investigated the infection kinetics of a 2007 UK BTV-8 strain alongside the re-emerging BTV-8 strain isolated from France in 2017. Two groups of eight BTV-naive British mule sheep were inoculated with 5.75 log10TCID50 ml-1 of either BTV-8 strain. BTV RNA was detected by 2 dpi in both groups with peak viremia occurring between 5-9 dpi. A significantly greater amount of BTV RNA was detected in sheep infected with the 2007 strain (6.0-8.8 log10 genome copies mL-1) than the re-emerging BTV-8 strain (2.9-7.9 log10 genome copies mL-1). All infected sheep developed BTV-specific antibodies by 9 dpi. BTV was isolated from 2 dpi to 12 dpi for 2007 BTV-8-inoculated sheep and from 5 to 10 dpi for sheep inoculated with the remerging BTV-8. In Culicoides sonorensis feeding on the sheep over the period 7-12 dpi, vector competence was significantly higher for the 2007 strain than the re-emerging strain. Both the proportion of animals showing moderate (as opposed to mild or no) clinical disease (6/8 vs 1/8) and the overall clinical scores (median 5.25 vs 3) were significantly higher in sheep infected with the 2007 strain, compared to those infected with the re-emerging strain. However, one sheep infected with the re-emerging strain was euthanized at 16 dpi having developed severe lameness. This highlights the potential of the re-emerging BTV-8 to still cause illness in naive ruminants with concurrent costs to the livestock industry.\n\nSummaryThe re-emerging Bluetongue virus serotype 8 still presents a threat to naive ruminants in Europe despite reduced virulence

epidemiology↗