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Ixodes ricinus ticks are Scandinavia's main vector for tick-borne encephalitis virus (TBEV), which infects many people annually. The aims of the present study were (i) to obtain information on the TBEV prevalence in host-seeking I. ricinus collected within the Øresund-Kattegat-Skagerrak (ØKS) region, which lies in southern Norway, southern Sweden and Denmark; (ii) to analyse whether there are potential spatial patterns in the TBEV prevalence; and (iii) to understand the relationship between TBEV prevalence and meteorological factors in southern Scandinavia. Tick nymphs were collected in 2016, in southern Scandinavia, and screened for TBEV, using pools of 10 nymphs, with RT real-time PCR, and positive samples were confirmed with pyrosequencing. Spatial autocorrelation and cluster analysis was performed with Global Moran's I and SatScan to test for spatial patterns and potential local clusters of the TBEV pool prevalence at each of the 50 sites. A climatic analysis was made to correlate parameters such as minimum, mean and maximum temperature, relative humidity and saturation deficit with TBEV pool prevalence. The climatic data were acquired from the nearest meteorological stations for 2015 and 2016. This study confirms the presence of TBEV in 12 out of 30 locations in Denmark, where six were from Jutland, three from Zealand and two from Bornholm and Falster counties. In total, five out of nine sites were positive from southern Sweden. TBEV prevalence of 0.7%, 0.5% and 0.5%, in nymphs, was found at three sites along the Oslofjord (two sites) and northern Skåne region (one site), indicating a potential concern for public health. We report an overall estimated TBEV prevalence of 0.1% in questing I. ricinus nymphs in southern Scandinavia with a region-specific prevalence of 0.1% in Denmark, 0.2% in southern Sweden and 0.1% in southeastern Norway. No evidence of a spatial pattern or local clusters was found in the study region. We found a strong correlation between TBEV prevalence in ticks and relative humidity in Sweden and Norway, which might suggest that humidity has a role in maintaining TBEV prevalence in ticks. TBEV is an emerging tick-borne pathogen in southern Scandinavia, and we recommend further studies to understand the TBEV transmission potential with changing climate in Scandinavia.

Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection., Funding agency:INTERREG-OKS Project ScandTick Innovation 20200422, Developvaccines@ORU

Tick-borne encephalitis virus (TBEV) is a Flavivirus which is transmitted to humans and animals by tick bites, and in rare cases by consumption of unpasteurised milk and dairy products. The virus can cause the disease tick-borne encephalitis (TBE), and lead to severe infection of the central nervous system in humans and animal species such as dogs and horses. TBEV is widespread in Europe and Asia, and an increasing number of TBE cases have been reported in the recent decades, including in Norway. The aims of this Ph.D.-thesis were to study the occurrence of: antibodies against TBEV in deer and cows, TBEV in unpasteurised cow’s milk in Norway, and to study co-infection of TBEV and the bacterium Anaplasma phagocytophilum in lambs by an experimental study. Skogflåttencefalittvirus (TBEV) er et Flavivirus som overføres til mennesker og dyr via flåttbitt, og i sjeldne tilfeller fra inntak av upasteurisert melk og andre meieriprodukter. Viruset kan forårsake sykdommen skogflåttencefalitt (TBE) og føre til alvorlig infeksjon i sentralnervesystemet hos mennesker og dyr som hund og hest. TBEV er utbredt i Europa og Asia, og det har blitt rapportert om et økende antall TBE-tilfeller de siste tiårene, også i Norge. Hensikten med denne doktorgradsavhandlingen var å studere forekomsten av: antistoffer mot TBEV i hjortedyr og kyr, TBEV i upasteurisert kumelk i Norge, og å studere koinfeksjon av TBEV og bakterien Anaplasma phagocytophilum i lam i en eksperimentell studie. The Ph.D.-project was funded by the following projects: “HiAbove - Highly infectious arthropod borne virus encephalitis” supported by the Norwegian University of Life Sciences, department of Production Animal Clinical Sciences, “Tick-borne diseases in the Barents region and western coast of Norway” (grant number B1412) and “EMERGING INFECTIONS: Capacity building on vector-borne infections in the Barents region, Norway and Russia-phase I” (grant number B1710) supported by the Norwegian Ministry of Health and Care Services, “Scandtick” (grant number 167116) supported by EU Interreg IV ØKS program and “Scandtick Innovation” (grant number 20200422) supported by the EU Interreg VA ØKS program.