Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis.

BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.

Control of ixodid ticks and prevention of tick-borne diseases in the United States: The prospect of a new Lyme disease vaccine and the continuing problem with tick exposure on residential properties.

In the United States, exposure to human-biting ixodid ticks can occur while spending time on residential properties or in neighborhood green spaces as well as during recreational or occupational activities on public lands. Human-biting tick species collectively transmit >15 species of pathogenic microorganisms and the national burden of tick-borne diseases is increasing. The prospect of a new Lyme disease vaccine for use in humans provides hope for substantial reduction in the >450,000 estimated annual cases of Lyme disease but this breakthrough would not reduce cases of other tick-borne diseases, such as anaplasmosis, babesiosis, ehrlichiosis, spotted fever group rickettsiosis, and Powassan encephalitis. One intriguing question is to what extent a new Lyme disease vaccine would impact the use of personal protection measures acting broadly against tick-bites. The main tick vector for Lyme disease spirochetes in the eastern United States, Ixodes scapularis, also transmits causative agents of anaplasmosis, babesiosis, and Powassan encephalitis; and this tick species co-occurs with other human-biting vectors such as Amblyomma americanum and Dermacentor variabilis. It therefore is important that a new Lyme disease vaccine does not result in reduced use of tick-bite prevention measures, such as tick repellents, permethrin-treated clothing, and frequent tick checks. Another key issue is the continuing problem with tick exposure on residential properties, which represents a heavily used outdoor environment the residents cannot reasonably avoid and where they tend to spend large amounts of time outside. As it may not be realistic to keep up daily vigilance with personal protective measures against tick-bites on residential properties during many months of every year, homeowners may also consider the option to suppress host-seeking ticks by means of deer fencing, landscaping, vegetation management, and use of products to kill host-seeking ticks or ticks infesting rodents. When considering the full range of options for actions that can be taken to suppress host-seeking ticks on residential properties, it is clear that individual homeowners face a difficult and bewildering task in deciding what to do based on very general guidance from public health agencies (developed without the benefit of a strong evidence base) and often without ready access to local public health professionals experienced in tick control. This situation is not satisfactory but cannot be corrected without first addressing knowledge gaps regarding the impact of peridomestic tick control measures on host-seeking ticks, human tick-bites, and tick-borne diseases. In parallel with this effort, there also is a need to increase the local public health workforce with knowledge of and experience with tick control to provide better access for homeowners to sound and objective advice regarding tick control on their properties based on key characteristics of the landscaping, habitat composition, and use patterns by wild animal tick hosts as well as the residents.

Omics and bioinformatics applied to vaccine development against Borrelia.

Borrelia burgdorferi is an extracellular spirochete that causes Lyme disease. Currently, no effective vaccine is available for humans and animals except for dogs. In the present study, an extensive bioinformatics pipeline was established to predict new candidates that can be used for vaccine development including building the protein-protein interaction network based on orthologues of experimentally verified protein-protein interaction networks, elucidation of the proteins involved in the immune response, selection of the topologically-interesting proteins and their prioritization based on their antigenicity. Proteomic network analysis yielded an interactome network with 120 nodes with 97 interactions. Proteins were selected to obtain a subnet containing only the borrelial membrane proteins and immune-related host proteins. This strategy resulted in the selection of 15 borrelial targets, which were subjected to extensive bioinformatics analysis to predict their antigenic properties. Based on the strategy applied in this study the proteins encoded by erpX (ErpX proteins, UniProt ID: H7C7L6), erpL (ErpL protein, UniProt ID: H7C7M3) and erpY (ErpY protein, UniProt ID: Q9S0D9) are suggested as a novel set of vaccine targets to control Lyme disease. Moreover, five different tools were used to validate their antigenicity regarding B-cells. The combination of all these proteins in a vaccine should allow improved protection against Borrelia infection.

Ixodes scapularis dystroglycan-like protein promotes Borrelia burgdorferi migration from the gut.

The causative agent of Lyme borreliosis, Borrelia burgdorferi, is transmitted by Ixodes ticks. During tick feeding, B. burgdorferi migrates from the tick gut to the salivary glands from where transmission to the host occurs. B. burgdorferi-interacting tick proteins might serve as vaccine targets to thwart B. burgdorferi transmission. A previous screening for B. burgdorferi-interacting Ixodes scapularis gut proteins identified an I. scapularis putative dystroglycan protein (ISCW015049). Here, we describe the ISCW015049's protein structure and its cellular location in the tick gut in relation to B. burgdorferi migration. Secondly, in vivo B. burgdorferi-tick attachment murine models were performed to study the role of ISCW015049 during B. burgdorferi migration and transmission. In silico analysis confirmed that ISCW015049 is similar to dystroglycan and was named I. scapularis dystroglycan-like protein (ISDLP). Confocal microscopy of gut tissue showed that ISDLP is expressed on the surface of gut cells, is upregulated during tick feeding, and is expressed significantly higher in infected ticks compared to uninfected ticks. Inhibition of ISDLP by RNA interference (RNAi) resulted in lower B. burgdorferi transmission to mice. In conclusion, we have identified a dystroglycan-like protein in I. scapularis gut that can bind to B. burgdorferi and promotes B. burgdorferi migration from the tick gut. Key messages: B. burgdorferi exploits tick proteins to orchestrate its transmission to the host. B. burgdorferi is able bind to an I. scapularis dystroglycan-like protein (ISDLP). Inhibition of ISDLP in ticks results in lower B. burgdorferi transmission to mice. ISDLP is a potential target to prevent Lyme borreliosis.

Lyme disease: Part II. Management and prevention.

Lyme disease (LD) is most often diagnosed clinically, and the differential diagnosis of erythema migrans may be challenging. Recent advances have raised questions about the efficacy of traditional diagnostic modalities, but may soon facilitate consistent identification of patients with Lyme borreliosis. Therapeutic recommendations vary with the stage of disease, and treatment usually leads to complete resolution. The management of patients with "chronic Lyme disease" is controversial. A number of preventative measures have been evaluated; those involving the avoidance of tick bites with protective clothing and insect repellents remain the simplest and most effective.

The Lyme disease vaccine--a public health perspective.

Lyme disease, which is caused by the spirochetal agent Borrelia burgdoferi, is the most common vector-borne illness in the United States. In 1998, the US Food and Drug Administration approved a recombinant Lyme disease vaccine that was later voluntarily withdrawn from the market by the manufacturer. Current Lyme disease prevention efforts focus on a combination of methods and approaches, including area acaricides, landscape management, host-targeted interventions, management of deer populations, and personal protective measures, such as the use of insect repellant and tick checks. Although these methods are generally safe and relatively inexpensive, the primary limitations of these methods are that their effectiveness has been difficult to demonstrate conclusively and that rates of compliance are generally poor. An effective human Lyme disease vaccine that has been adequately evaluated in the highest-risk population groups could be very beneficial in preventing Lyme disease; however, it would need to meet high standards regarding safety, efficacy, cost, and public acceptance.

Strategies for primary and secondary prevention of Lyme disease.

Lyme disease (borreliosis) incidence continues to increase despite a growing knowledge of primary and secondary prevention strategies. Primary prevention aims to reduce the risk of tick exposure and thereby decrease the incidence of new Lyme disease cases. Secondary prevention targets the development of disease or reduces disease severity among people who have been bitten by infected ticks. Numerous prevention strategies are available, and although they vary in cost, acceptability and effectiveness, uptake has been universally poor. Research in areas where Lyme disease is endemic has demonstrated that despite adequate knowledge about its symptoms and transmission, many people do not perform behaviors to reduce their risk of infection. New prevention strategies should aim to increase people's confidence in their ability to carry out preventive behaviors, raise awareness of desirable outcomes, and aid in the realization that the necessary skills and resources are available for preventive measures to be taken. In this article we evaluate the prevention and treatment strategies for Lyme disease, and discuss how these strategies can be implemented effectively. As many patients with Lyme disease develop arthritis and are referred to rheumatologists it is important that these health-care providers can educate patients about disease-prevention strategies.

An evaluation of a Lyme disease prevention program in a working population.

PURPOSE: Lyme disease vaccine was offered to New York State Department of Health employees considered at risk for Lyme disease because of their job duties. This evaluation was conducted to assess (1) attitudes that affected employees' decisions to accept or decline the vaccine, (2) preventive behaviors among employees who received the vaccine, and (3) effectiveness of the educational modalities offered in improving knowledge of Lyme disease and Lyme disease vaccine. METHODS: A total of 190 eligible employees were identified and were offered two educational modalities before deciding whether to receive the vaccine. The subsequent evaluation involved three telephone interviews, one pre-education and two posteducation-vaccination, to assess factors affecting the decision about vaccination and attitudes, behaviors, and knowledge among vaccine recipients (N=30) and nonrecipients (N=160). RESULTS: This evaluation indicated that the majority of vaccine recipients decided to receive the vaccine because of an anticipated risk of tick exposure. For employees who declined vaccination, many were concerned about the safety (64%), novelty (56%), or efficacy (48%) of the vaccine. Posteducation knowledge of Lyme disease vaccine significantly improved among those who attended an education session compared with those who did not and was retained 1 year later. DISCUSSION: The results suggest that when a vaccine-related disease-prevention program is undertaken, (1) attitudes about disease risks and vaccine risks influence decisions to accept vaccination, and (2) in-person education should be a mandatory element of the program.

[Lyme borreliosis]. / La maladie de Lyme.

Lyme disease is a multisystemic disease caused by a spirochete, Borrelia Burgdorferi that is transmitted by ticks. A clinical diagnosis is easy when a tick bite is followed 3 weeks later by erythema migrans, than by involvement of nervous system, joints or heart. In case of neuroborreliosis, serological tests, performed in blood and cerebro-spinal fluid, support the diagnosis and patients recover rapidly with antibacterial treatments. However an accurate diagnosis remains sometimes problematic, especially distinction between a coincidental positive serologic test and a nervous system Lyme borreliosis which require antibiotics. Furthermore, the role of autoimmunity in the pathophysiology of late Lyme disease, antibiotic choice in early disease, duration of treatment, and utility of vaccination are discussed.

Current and future treatment of Lyme disease.

Lyme borreliosis, a tick-transmitted spirochetal disease, may begin with a characteristic expanding skin lesion at the site of the tick bite. Within several days to weeks, the infection can spread haematogenously to involve the heart, nervous system or the joints. After months to years, the spirochete may persist in these organs causing a chronic form of illness. All stages of this disease can be treatable with antimicrobial agents.

Lyme disease.

PURPOSE: To review the presentation, treatment, and prevention of Lyme disease in primary care. DATA SOURCES: Selected articles from the scientific literature and the Centers for Disease Control. CONCLUSIONS: Lyme disease is a tick-borne, multisystem inflammatory disease with worldwide distribution caused by the spirochete Borrelia burgdorferi. Lyme disease is initially characterized by a spreading, annular erythema migrans skin rash and can disseminate to the musculoskeletal, neurologic, or cardiovascular system. Stages of the disease present with varying clinical manifestations. IMPLICATIONS FOR PRACTICE: Treatment of Lyme disease with appropriate antimicrobial therapy should be prompt in order to avoid debilitating outcomes. Awareness of the many presentations of Lyme disease in endemic areas may facilitate a timely diagnosis and appropriate treatment.