Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches.

Lyme disease is caused by the spirochete, Borrelia burgdorferi, which is transmitted by Ixodes spp ticks. The rise in Lyme disease cases since its discovery in the 1970s has reinforced the need for a vaccine. A vaccine based on B burgdorferi outer surface protein A (OspA) was approved by the Food and Drug Administration (FDA) several decades ago, but was pulled from the market a few years later, reportedly due to poor sales, despite multiple organizations concluding that it was safe and effective. Newer OspA-based vaccines are being developed and are likely to be available in the coming years. More recently, there has been a push to develop vaccines that target the tick vector instead of the pathogen to inhibit tick feeding and thus prevent transmission of tick-borne pathogens to humans and wildlife reservoirs. This review outlines the history of Lyme disease vaccines and this movement to anti-tick vaccine approaches.

The effect of fluralaner treatment of small mammals on the endemic cycle of Borrelia burgdorferi in a natural environment.

Among approaches aimed at reducing Lyme disease risk in the environment, those targeting reservoirs of Borrelia burgdorferi Johnson are promising because they have the potential to reduce both the density of questing Ixodes scapularis Say (Acari: Ixodidea) ticks and the prevalence of B. burgdorferi in the tick population. In this 4-yr field study, we treated a population of wild small mammals with 2 densities of fluralaner baits and investigated the effect of the treatment on 3 parameters of the endemic cycle of B. burgdorferi: (i) the prevalence of infected Peromyscus mice (PIM), (ii) the density of questing nymphs (DON), and (iii) the prevalence of infected questing nymphs (NIP). We demonstrated that fluralaner baiting is effective at reducing tick infestation of Peromyscus mice, the main reservoir of B. burgdorferi in central and northeastern North America, in the laboratory and the field. Results from this study showed a significant decrease in B. burgdorferi infection in mice (odds ratio: 0.37 [CI95: 0.17 to 0.83]). A reduction in the DON between 45.4% [CI95: 22.4 to 61.6] and 62.7% [CI95: 45.9 to 74.2] occurred in treated area when compared with control areas. No significant effect was reported on the NIP. These results confirm the hypothesis that fluralaner baits have an effect on B. burgdorferi endemic cycle, with the potential to reduce the density of B. burgdorferi-infected ticks in the environment. Further studies performed in various habitats and public health intervention contexts are needed to refine and operationalize this approach for reducing Lyme disease risk in the environment.

Modeling platform to assess the effectiveness of single and integrated Ixodes scapularis tick control methods.

BACKGROUND: Lyme disease continues to expand in Canada and the USA and no single intervention is likely to curb the epidemic. METHODS: We propose a platform to quantitatively assess the effectiveness of a subset of Ixodes scapularis tick management approaches. The platform allows us to assess the impact of different control treatments, conducted either individually (single interventions) or in combination (combined efforts), with varying timings and durations. Interventions include three low environmental toxicity measures in differing combinations, namely reductions in white-tailed deer (Odocoileus virginianus) populations, broadcast area-application of the entomopathogenic fungus Metarhizium anisopliae, and fipronil-based rodent-targeted bait boxes. To assess the impact of these control efforts, we calibrated a process-based mathematical model to data collected from residential properties in the town of Redding, southwestern Connecticut, where an integrated tick management program to reduce I.xodes scapularis nymphs was conducted from 2013 through 2016. We estimated parameters mechanistically for each of the three treatments, simulated multiple combinations and timings of interventions, and computed the resulting percent reduction of the nymphal peak and of the area under the phenology curve. RESULTS: Simulation outputs suggest that the three-treatment combination and the bait boxes-deer reduction combination had the overall highest impacts on suppressing I. scapularis nymphs. All (single or combined) interventions were more efficacious when implemented for a higher number of years. When implemented for at least 4 years, most interventions (except the single application of the entomopathogenic fungus) were predicted to strongly reduce the nymphal peak compared with the no intervention scenario. Finally, we determined the optimal period to apply the entomopathogenic fungus in residential yards, depending on the number of applications. CONCLUSIONS: Computer simulation is a powerful tool to identify the optimal deployment of individual and combined tick management approaches, which can synergistically contribute to short-to-long-term, costeffective, and sustainable control of tick-borne diseases in integrated tick management (ITM) interventions.

Antibody-mediated immunological memory correlates with long-term Lyme veterinary vaccine protection in mice.

Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the United States. Despite the rise in Lyme disease incidence, there is no vaccine against B. burgdorferi approved for human use. Little is known about the immune correlates of protection needed to prevent Lyme disease. In this work, a mouse model was used to characterize the immune response and compare the protection provided by two USDA-approved vaccines for use in canines: Duramune (bacterin vaccine) and Vanguard crLyme (subunit vaccine composed of two outer surface proteins, OspA and OspC). C3H/HeNCrl mice were immunized with two doses of either Duramune or Vanguard, and immune responses and protection against B. burgdorferi were assessed in short (35 days) and long-term (120 days) studies. Flow cytometry, ELISPOT detection of antibody-producing cells, and antibody affinity studies were performed to identify correlates of vaccine-mediated protection. Both vaccines induced humoral responses, with high IgG titers against B. burgdorferi. However, the levels of anti-B. burgdorferi antibodies decayed over time in Vanguard-vaccinated mice. While both vaccines triggered the production of antibodies against both OspA and OspC, antibody levels against these proteins were also lower in Vanguard-vaccinated mice 120 days post-vaccination. Both vaccines only provided partial protection against B. burgdorferi at the dose used in this model. The protection provided by Duramune was superior to Vanguard 120 days post-vaccination, and was characterized by higher antibody titers, higher abundance of long-lived plasma cells, and higher avidity antibodies than Vanguard. Overall, these studies provide insights into the importance of the humoral memory response to veterinary vaccines against Lyme disease and will help inform the development of future human vaccines.

Trending ticks: using Google Trends data to understand tickborne disease prevention.

Introduction: Ticks and pathogens they carry seriously impact human and animal health, with some diseases like Lyme and Alpha-gal syndrome posing risks. Searching for health information online can change people's health and preventive behaviors, allowing them to face the tick risks. This study aimed to predict the potential risks of tickborne diseases by examining individuals' online search behavior. Methods: By scrutinizing the search trends across various geographical areas and timeframes within the United States, we determined outdoor activities associated with potential risks of tick-related diseases. Google Trends was used as the data collection and analysis tool due to its accessibility to big data on people's online searching behaviors. We interact with vast amounts of population search data and provide inferences between population behavior and health-related phenomena. Data were collected in the United States from April 2022 to March 2023, with some terms about outdoor activities and tick risks. Results and Discussion: Results highlighted the public's risk susceptibility and severity when participating in activities. Our results found that searches for terms related to tick risk were associated with the five-year average Lyme Disease incidence rates by state, reflecting the predictability of online health searching for tickborne disease risks. Geographically, the results revealed that the states with the highest relative search volumes for tick-related terms were predominantly located in the Eastern region. Periodically, terms can be found to have higher search records during summer. In addition, the results showed that terms related to outdoor activities, such as "corn maze," "hunting," "u-pick," and "park," have moderate associations with tick-related terms. This study provided recommendations for effective communication strategies to encourage the public's adoption of health-promoting behaviors. Displaying warnings in the online search results of individuals who are at high risk for tick exposure or collaborating with outdoor activity locations to disseminate physical preventive messages may help mitigate the risks associated with tickborne diseases.

A rodent and tick bait for controlling white-footed mice (Peromyscus leucopus) and blacklegged ticks (Ixodes scapularis), the respective pathogen host and vector of the Lyme disease spirochetes.

A promising alternative approach to conventional vector and rodent control practices is the use of a bait containing a rodenticide and acaricide in controlling vectors and pathogen reservoirs concurrently. In the United States, Lyme disease continues to be the most prevalent vector-borne disease with approximately 500,000 Lyme disease cases estimated each year. Previous research has demonstrated the usefulness of a low dose fipronil bait in controlling Ixodes scapularis larvae feeding on white-footed mice. However, considering white-footed mice can be an unwanted species because of their association with tick-borne disease and hantaviruses, a combination rodent and tick bait (RTB) might provide a useful alternative to encourage additional community participation in integrated tick management (ITM) efforts. The purpose of this research was to evaluate the use of RTB (0.025 % warfarin, 0.005 % fipronil) in controlling white-footed mice and I. scapularis larvae. Studies were designed in part based on Environmental Protection Agency (EPA) guidelines. A laboratory choice test was conducted to evaluate the use of RTB in controlling white-footed mice over 15-day exposure when they were exposed to an alternative diet. Mice were observed every day for mortality and signs of warfarin toxicity. A simulated field test was conducted to evaluate the use of RTB, presented in the presence of an alternative diet, in controlling I. scapularis parasitizing white-footed mice over 4-day exposure. Mice were fitted with capsules and manually infested with I. scapularis larvae. The inside of each capsule was observed to evaluate tick attachment. Replete larvae detaching from each mouse were collected. Blood was collected from all treatment group mice via cardiac puncture to determine the fipronil sulfone concentration in plasma for each animal. Results indicated that RTB would be adequately consumed in the presence of an alternative diet under laboratory and simulated field conditions. Treatment with RTB resulted in 100 % mortality of white-footed mice during 15-day exposure and prevented 100 % larvae from feeding to repletion during 4-day exposure. All mice succumbing to RTB showed signs of warfarin toxicity. All mice parasitized with ticks that were exposed to RTB had fipronil sulfone detectable in plasma, with even the lowest concentration detected (8.1 parts per billion) controlling 100 % parasitizing I. scapularis larvae. The results suggest that RTB could be a useful means of rodent and tick control for use in ITM programs.

Optimisation of dose level and vaccination schedule for the VLA15 Lyme borreliosis vaccine candidate among healthy adults: two randomised, observer-blind, placebo-controlled, multicentre, phase 2 studies.

BACKGROUND: Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1-6, which are associated with the most common pathogenic Borrelia species in Europe and North America. METHODS: Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18-65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 µg (study one only), 135 µg, or 180 µg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 µg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed. FINDINGS: For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 µg VLA15, 215 to 135 µg, 205 to 180 µg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 µg VLA15, 100 to 180 µg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4-119·0) to 267·4 units per mL (serotype 3; 194·8-367·1) for 90 µg VLA15, 101·9 (serotype 1; 87·1-119·4) to 283·2 units per mL (serotype 3; 248·2-323·1) for 135 µg, and 115·8 (serotype 1; 98·8-135·7) to 308·6 units per mL (serotype 3; 266·8-356·8) for 180 µg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9-361·0) to 545·2 units per mL (serotype 2; 431·8-688·4) for 135 µg VLA15 and 274·7 (serotype 1; 209·4-360·4) to 596·8 units per mL (serotype 3; 471·9-754·8) for 180 µg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91-96 vs 26%, 19-34; study two: 96%, 93-98 vs 35%, 24-49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65-73 vs 43%, 34-52; study two: 74%, 67-80 vs 51%, 38-64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48-57) of participants in the VLA15 groups and 52% (43-60) of those in the placebo groups; for study two these were 65% (58-71) and 69% (55-80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1-4; study two: 4%, 2-7) and adverse events of special interest (study one: 1%, 0-2; study two: 1%, 0-3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported. INTERPRETATION: VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 µg dose and 0-2-6-month schedule, which was associated with the greatest immune responses. FUNDING: Valneva.

Lime for Lyme: Treatment of Leaf Litter with Dolomitic Lime Powder Impairs Activity of Immature Ixodes scapularis Ticks.

Background: Tick-borne diseases are an emerging threat to public health throughout the temperate world, leading to a growing field of research aimed at developing and testing intervention strategies for reducing human-tick encounters or prevalence of infection in ticks. Various wide-spectrum chemical acaricides have proven effective for controlling tick populations, but many of these have potential deleterious side-effects on health and the environment. In addition to chemical acaricides, certain compounds such as diatomaceous earth have been shown to have physical acaricidal properties. We hypothesized that dolomitic lime (CaMg(CO3)2, a corrosive, desiccant mineral that is already used extensively in agricultural and forestry contexts to balance the pH of soils, may affect ticks' locomotory activity, habitat position, or survival and that this should manifest as a reduction in the number of questing ticks collected by dragging. Objective: This study aimed to formally assess this hypothesis in a controlled laboratory setting. Methods: We carried out a microcosm experiment, with one control and three treated microcosm trays, each replicating the natural substrate characterizing I. scapularis habitat in northeastern North America. Each tray was infested with 200 living larvae and 50 nymphs, and then treated with 0 (control), 50, 100, or 500 g/m2 of lime powder. Ticks were collected by microdragging 24 and 72 h postliming. Results: Efficacy of liming at reducing the number of collected questing ticks ranged from 87% to 100% for larvae and 0% to 69% for nymphs 24 h postliming and from 91% to 93% for larvae and -47% to 65% for nymphs 72 postliming. Conclusion: This study provides the first experimental evidence of the potential efficacy of liming for impairing activity of questing immature ticks. Given that lime is a low-cost material, that methods for widespread application in deciduous woodlands already exist, and that it has been documented as having a limited negative impact on the environment, further assessment of lime application as a public health risk reduction intervention for tick-borne diseases is warranted.

Using the Health Belief Model to understand intention to vaccinate for Lyme disease in the United States.

AIMS: A growing number of Lyme disease (LD) cases in the U.S. are reported in states neighbouring those with high-incidence (>10 cases per 100,000 population) rates. Considering the evolving epidemiology, high-incidence counties in many of these "neighbouring states," and the forthcoming vaccines, understanding the drivers of vaccination intention is critical, particularly how drivers of intention in neighbouring states vary relative to regions currently classified as high incidence. This study uses the Health Belief Model (HBM) to determine the key drivers associated with vaccine intention for U.S. adults and caregivers of children residing in neighbouring states. METHODS AND RESULTS: Using an established panel with quotas for age, sex, race/ethnicity and urbanity, we surveyed 887 adults and 822 caregivers of children residing in U.S. neighbouring states. Survey items included measures of intention and HBM constructs, all of which were assessed using 5-point Likert scales. We subsequently used structural equation modelling to understand the influence of the HBM constructs on LD vaccine intention. Estimates from structural equation modelling show that the HBM constructs explain much of the variation in intention to vaccinate against LD. Intentions to vaccinate for both adults and caregivers are positively influenced by cues to action, perceived susceptibility of LD, and perceived benefits to vaccination. Both are also negatively influenced by perceived barriers to vaccination. The caregiver's intention to vaccinate is also positively influenced by the perceived severity of LD. CONCLUSION: The intention to vaccinate for respondents residing in LD neighbouring states is strongly influenced by recommendations from healthcare providers or the Centers for Disease Control and Prevention (CDC). As incidence rises in neighbouring states and the need to prevent disease becomes more overt, public health officials should strongly recognize the influence of healthcare providers and CDC recommendations on intention to vaccinate against LD.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario.

BACKGROUND: The number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region. METHODS: A geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period. RESULTS: 60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31). CONCLUSIONS: This study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).

Camelid-derived, single-domain antibodies (VHHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed VHH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from Borrelia burgdorferi sensu stricto strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment ("panning") against recombinant OspA, yielding 21 unique VHHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent VHHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including B. burgdorferi agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The VHHs displayed unique reactivity profiles with the seven OspA serotypes associated with B. burgdorferi genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.

Lyme disease vaccine attitudes and intentions among parents of children aged 5-18 years in the United States.

BACKGROUND: Lyme disease (LD) is the most common vector-borne disease in the United States, with increasing incidence and geographic range. Case incidence peaks among school-aged children. New LD preventives are in clinical trials. METHODS: We conducted an online survey of parents of children aged 5-18 years in states with high or emerging incidence of LD. Our primary outcome was willingness ("definitely" or "probably") for their child to receive an LD vaccine. Our secondary outcome was preference for annual monoclonal antibody injections compared to a 3-dose vaccine series with boosters. Analyses were weighted to reflect parent gender, parent race/ethnicity, and child age by state. RESULTS: Among 1,351 parent respondents, most (68.0 %) would have their child vaccinated against LD, with significantly more being willing in high compared to emerging incidence states (70.4 % versus 63.6 %, p = 0.027). Of parents who were unsure or unwilling, 33.5 % and 16.5 %, respectively, would do so with a provider recommendation. Vaccine safety concerns were among the top reasons for LD vaccine hesitancy. More parents preferred a pre-formed antibody (42.3 %) compared to a 3-dose vaccine series (34.7 %). Significant predictors of willingness to have one's child vaccinated were higher parental education; higher perceived risk of child getting LD; child spending time outdoors daily or weekly; following a regular vaccine schedule; and positive attitude towards vaccines. Significant predictors of preference for monoclonal antibody over a 3-dose vaccine series included prior awareness of LD, living in a rural area, and less positive attitudes towards vaccines. CONCLUSIONS: Two-thirds of parents in high and emerging incidence states would vaccinate their children against Lyme disease. Addressing safety concerns will be important, and a health care provider recommendation could also encourage those who are unsure or unwilling. Given the slight preference for monoclonal antibody over vaccine, particularly in rural areas, access to both may increase LD prevention.

Biophysical and biochemical characterization of a recombinant Lyme disease vaccine antigen, CspZ-YA.

Lyme disease, caused by Lyme Borrelia spirochetes, is the most common vector-borne illness in the United States. Despite its global significance, with an estimated 14.5 % seroprevalence, there is currently no licensed vaccine. Previously, we demonstrated that CspZ-YA protein conferred protection against Lyme Borrelia infection, making it a promising vaccine candidate. However, such a protein was tagged with hexahistidine, and thus not preferred for vaccine development; furthermore, the formulation to stabilize the protein was understudied. In this work, we developed a two-step purification process for tag-free E. coli-expressed recombinant CspZ-YA. We further utilized various bioassays to analyze the protein and determine the suitable buffer system for long-term storage and formulation as a vaccine immunogen. The results indicated that a buffer with a pH between 6.5 and 8.5 stabilized CspZ-YA by reducing its surface hydrophobicity and colloidal interactions. Additionally, low pH values induced a change in local spatial conformation and resulted in a decrease in α-helix content. Lastly, an optimal salinity of 22-400 mM at pH 7.5 was found to be important for its stability. Collectively, this study provides a fundamental biochemical and biophysical understanding and insights into the ideal stabilizing conditions to produce CspZ-YA recombinant protein for use in vaccine formulation and development.

Intention to vaccinate for Lyme disease using the Health Belief Model.

AIMS: Lyme disease (LD) cases in the United States are estimated to be approaching 500,000 annually. Protective measures, such as repellent use and wearing protective clothing are recommended by public health officials. However, no protective measure has been proven to be consistently effective, partly because they require consistent and persistent behaviour change. While safe and effective vaccines are in development, it is unclear what factors influence the intention to vaccinate against LD. This study uses the Health Belief Model (HBM) framework to determine key drivers associated with vaccine intention. The HBM is widely applied in public health research and uses the following constructs: perceived susceptibility and severity of disease, perceived benefits and barriers to disease prevention, and cues to action for disease prevention to predict health behaviours. To date, the HBM framework has not been applied to vaccination intention for LD. METHODS AND RESULTS: Data were collected from 874 adults and 834 caregivers of children residing in US states endemic to LD. Sampling adults and caregivers allows us to explore how the intention to vaccinate differs among those at-risk. Estimates from structural equation modelling (SEM) show that the HBM constructs explain much of the variation in intention to vaccinate against LD. Both adult and caregiver intentions to vaccinate are positively influenced by cues to action, perceived susceptibility of LD, and perceived benefits to vaccination. However, there is variation in the influence of constructs across the samples. Caregiver's intention to vaccinate is positively influenced by the perceived severity of LD and negatively influenced by safety concerns about the vaccine, whereas adult intention is negatively influenced by perceived barriers to vaccination. CONCLUSION: A strong relationship of cues to action on vaccine intention in samples of adults and caregivers suggests the importance of a recommendation from a healthcare provider or the Centers for Disease Control and Prevention (CDC).

Operational Considerations for Using Deer-Targeted 4-Poster Tick Control Devices in a Tick-borne Disease Endemic Community.

CONTEXT: In the northeastern United States, recommendations to prevent diseases spread by black-legged ticks ( Ixodes scapularis ) and lone star ticks ( Amblyomma americanum ) often rely on individuals to use personal protection or yard-based strategies. The 4-Poster deer treatment stations (4-Posters) suppress tick populations by treating deer hosts with acaricide, potentially offering a community-wide approach for reducing tick-borne diseases in endemic areas. The 4-Poster deployment logistics in mainland community settings are not well documented but are needed for future public health tick control efforts. PROGRAM: As part of a public health research effort to design a population-based 4-Poster effectiveness study aimed at reducing tick-borne disease incidence, TickNET researchers partnered with the Town of Ridgefield (Connecticut) to understand the feasibility and operational logistics of deploying 4-Posters on public land within a residential community to inform future public health interventions by municipalities or vector control agencies. IMPLEMENTATION: We deployed three 4-Posters on a municipal property from July to December 2020 and used motion-activated cameras to record wildlife activity nearby. We documented per-device operational details, costs, materials consumed, and animal activity. EVALUATION: Operation of 4-Posters was feasible, and device challenges were easily remedied. Deer visitation and heavy nontarget animal use were documented at all devices. Unexpectedly, monthly corn consumption was not correlated with monthly deer-view days. The monthly cost per device was US $1279 or US $305 per hectare with an average 21 minutes of weekly service time. DISCUSSION: Use of 4-Posters by communities, public health agencies, or vector control programs may be a practicable addition to tick management programs in tick-borne disease endemic areas in the Northeast. Such programs should carefully consider local and state regulations, follow manufacturer and pesticide label guidelines, and include wildlife monitoring. High labor costs incurred in this project could be mitigated by training vector control agency or municipality staff to service 4-Posters.

Prospective incidence epidemiology study protocol: conducting active surveillance to assess the burden of Lyme disease (BOLD) in primary care practices in endemic areas of six European countries.

INTRODUCTION: Lyme disease (LD) is the most frequent tick-borne disease in the moderate climates of Europe. This study will inform the phase III efficacy study for Pfizer and Valneva's investigational Lyme disease vaccine, VLA15. VLA15 phase III will be conducted in the USA and Europe due to the vaccine's serotype coverage and public health burden of LD. In Europe, the existence and location of sites that have access to populations with high LD annual incidence is uncertain. This active, prospective surveillance study assesses annual LD incidence at general practice (GP)/primary care sites, allowing for phase III site vetting and better characterisation of LD burden in selected regions for study size calculations. METHODS AND ANALYSIS: This burden of Lyme disease (BOLD) study will assess LD incidence overall and by site at 15 GP/primary care practices in endemic areas of 6 European countries from Spring 2021 to December 2022 and will be summarised with counts (n), percentages (%) and associated 95% CIs. Suspected LD cases identified from site's practice panels are documented on screening logs, where clinical LD manifestations, diagnoses and standard of care diagnostic results are recorded. In the initial 12-month enrolment phase, suspected LD cases are offered enrolment. Participants undergo interview and clinical assessments to establish medical history, final clinical diagnosis, clinical manifestations and quality of life impact. Study-specific procedures include LD serology, skin punch biopsies and Lyme manifestation photographs. For every enrolled participant diagnosed with LD, 6-10 age-matched controls are randomly selected and offered enrolment for an embedded LD risk factor analysis. Persistent symptoms or post-treatment LD will be assessed at follow-up visits up to 2 years after initial diagnosis, while patients remain symptomatic. ETHICS AND DISSEMINATION: This study has been approved by all sites' local ethics committees. The results will be presented at conferences and published in peer-reviewed journals.

Lyme Disease Knowledge, Practices, and Vaccine Acceptability Among Nurse Practitioners in Pediatric Practice.

INTRODUCTION: Lyme disease (LD) is a major public health problem in the United States. Given its incidence and geographic expansion, nurse practitioners (NPs) will likely encounter patients with this condition. METHOD: NPs were invited to participate in an electronic survey via email, newsletter, and social media posts. The 31-question survey collected information on provider characteristics, clinical scenario decisions, resources used, and vaccine sentiment for LD. RESULTS: Survey participants (n = 606) were primarily cisgender female (75%) and aged 30-49 years (62%). Responding to six hypothetical clinical scenarios, only 31% of participants answered most questions correctly. If an LD vaccine becomes available, 39% said they would incorporate it into practice; 48% would seek further information before deciding. DISCUSSION: Additional education on LD prevention, diagnosis, and treatment is needed for NPs. Increasing provider awareness of current guidelines and developing tailored resources for NPs may improve patient care.

Knowledge, protection behaviours and seroprevalence of Lyme borreliosis in inhabitants of Lublin Province, eastern Poland - evaluation of a prophylaxis programme.

INTRODUCTION AND OBJECTIVE: Lyme borreliosis (LB) is the most frequent tick-borne disease with 17,338 cases reported in Poland in 2022. Since research on a LB vaccine is still ongoing, the promotion of individual behaviours and limiting of tick exposure is one of the most effective ways to prevent LB. The aim of the study was to evaluate the effectiveness of the LB prevention programme by assessing the knowledge, practice behaviours, seroprevalence of LB and satisfaction among the population of the Lublin Province in eastern Poland. MATERIAL AND METHODS: The prevention programme was carried out among 2,920 participants who were asked about their exposure to ticks, history of LB and prevention behaviours. Awareness of knowledge was evaluated before and after training. Seroprevalence of LB was rated by ELISA and immunoblot assays. RESULTS: Over 73% of participants reported tick bites in their lifetime, without significant differences between rural and urban area inhabitants. More than 80% of individuals declared that they use protective measures (PPM), such as proper clothes and body checking; repellents were the least frequently used by participants. The diagnosis of LB but not tick bites in a lifetime influenced the more frequent use of PPM. Increase in knowledge was observed in 86% of participants after education, and the highest knowledge was noted among respondents with higher education. The seroprevalence of anti-B. burgdorferi antibodies was 37% and was higher among men than women (40% vs. 36%). CONCLUSIONS: The population of Lublin Province is highly exposed to tick bites and infection with B. burgdorferi. The high seroprevalence and increase in knowledge confirmed the effectiveness and need for preventive programmes. These results can be useful for optimizing and enhancing the effects of future prevention campaigns.

Development of an mRNA-lipid nanoparticle vaccine against Lyme disease.

Lyme disease is the most common vector-borne infectious disease in the United States, in part because a vaccine against it is not currently available for humans. We propose utilizing the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform to generate a Lyme disease vaccine like the successful clinical vaccines against SARS-CoV-2. Of the antigens expressed by Borrelia burgdorferi, the causative agent of Lyme disease, outer surface protein A (OspA) is the most promising candidate for vaccine development. We have designed and synthesized an OspA-encoding mRNA-LNP vaccine and compared its immunogenicity and protective efficacy to an alum-adjuvanted OspA protein subunit vaccine. OspA mRNA-LNP induced superior humoral and cell-mediated immune responses in mice after a single immunization. These potent immune responses resulted in protection against bacterial infection. Our study demonstrates that highly efficient mRNA vaccines can be developed against bacterial targets.