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Lyme disease (LD) is the most common vector-borne disease caused by Borrelia, which is transmitted to humans through the bite of infected ticks. There are four main species of Borrelia: B. burgdorferi and B. mayonii which cause most Lyme disease infections in the United States, and B. afzelii and B. garinii which are the leading causes in Europe and Asia. Nymphal ticks are a key source of human infection with Borrelia burgdorferi and typically feed in the late spring or early summer, which produces a June–July peak in human illness. Early symptoms of Lyme disease (such as a gradually expanding erythematous rash called Erythema migrans or more nonspecific symptoms like fatigue, fever, headache, mild stiff neck, arthralgia or myalgia) are often overlooked or misinterpreted. Left untreated, the disease can disseminate and cause more serious complications affecting the joints (arthritis), the heart (carditis) or the nervous system. While the true incidence of Lyme disease is unknown, it is estimated to annually affect approximately 476,000 people in the United States and 130,000 people in Europe.
B. burgdorferi has a flat-wave morphology, is ~300 nm in diameter and 10-30 μm in length. The cell envelope of B. burgdorferi consists of a protoplasmic cylinder covered by two lipid membranes. Between the outer and inner membrane is the periplasmic space that comprises the peptidoglycan layer and flagellar filaments. The general structure of B. burgdorferi's cell envelope differs significantly from the typical Gram-negative bacteria. LPSs are usually outer membrane components of Gram-negative bacteria; however, B. burgdorferi lacks LPS, and has immunoreactive glycolipids instead. The defining characteristic of B. burgdorferi is the periplasmic flagella, which are provide motility functions as well as confine the shape of the cell. The flagella are attached to each cell pole and wind around the cell cylinder in the periplasmic space between the peptidoglycan layer and the outer membrane. Flagellar motors are located at the cell poles and are situated next to the methyl-accepting chemotaxis proteins that direct the movement of the bacteria towards chemoattractants and away from repellants.
Fig. 1. Morphology of Borrelia burgdorferi (Steere AC, et al. 2016)
All genospecies of the B. burgdorferi complex have small, highly segmented genomes. The B. burgdorferi strain B31 has a genome size of 1.5 million bases. This genome consists of a linear chromosome of 910 kilobases, 9 linear plasmids and 12 circular plasmids of different sizes. The linear chromosome is typically conserved among different B. burgdorferi genospecies, while the plasmids exhibit a higher degree of variation. The chromosome of B. burgdorferi carries the main genes essential for maintaining survival and replication in the tick and the vertebrate host but is devoid of genes encoding enzymes for de novo synthesis of amino acids, fatty acids, enzyme cofactors, and nucleic acids. Therefore, B. burgdorferi has a very limited metabolic capacity and is highly dependent on its tick vector and vertebrate host for many essential factors. Virulence determinants of B. burgdorferi are found both on the linear chromosome and on linear and circular plasmids. Chromosomal virulence genes include p66, bgp, plzA, rpoN, rpoS, or bosR whereas virulence-associated genes that are present on plasmids encode proteins such as DbpA/B, BBK32, OspC, PncA, VlsE. Factors important for bacterial survival in a mammalian host can be subdivided into two groups. Some are involved in early infection, such as OspC, which are presumably required for host colonization or resistance to innate immunity. Others are involved in resistance to acquired immunity, such as VlsE.
Fig. 2. Cellular architecture of Borrelia burgdorferi (Steere AC, et al. 2016).
In both the United States and Europe, serological testing is the only practical and readily available method to support a diagnosis of Lyme borreliosis. The detection of antibodies to B. burgdorferi, determined by ELISA and western blotting. The ELISA provides a quantitative estimate of the concentration of antibodies against B burgdorferi. The western blotting provides qualitative information about the specificity of the antibodies. Official recommendation from the CDC is that clinicians should use a two-step process when ordering antibody tests for Lyme disease. First, a serologic ELISA screening assay should be performed and any positive or indeterminate results should be confirmed by western blotting to detect IgM and IgG antibodies to Borrelia. The presence of antibodies against at least either 2 (for IgM) or 5 (for IgG) proteins of B burgdorferi are required for the immunoblot result to be considered positive.
Fig. 3. Points at which interruption of B. burgdorferi transmission to humans can be achieved through vaccination. (Rouphael NG, et al. 2011).
The discussion regarding new vaccine candidates and strategies focused on host immunity and the triad comprising bacteria, the tick, and vertebrate reservoirs. How the bacteria can be targeted by additional vaccine candidates for direct application to humans and animals, how to disrupt transmission within the agents that maintain the enzootic cycle of B. burgdorferi (the tick and the reservoir), and how these indirect strategies would impact incidence of B. burgdorferi infection in accidental hosts (humans and domestic animals).
OspA is a lipoprotein expressed by bacteria when present in a tick. Antibodies against OspA, acquired with the blood meal as the tick feeds on vaccinated hosts, bind and kill the organism in the tick midgut before transmission can take place. Therefore, blocking OspA inhibits the bacterium's ability to leave the tick and infect humans. The first and only licensed vaccine against Lyme disease, called LYMERix, was a recombinant OspA vaccine (now GlaxoSmithKline). This was about 78% effective in protecting against Lyme infection after all three doses of the vaccine were given. The vaccine was licensed in 1998. By 2002, SmithKline Beecham had withdrawn it from the market citing poor market performance. VLA15 (Valneva and Pfizer) is the only Lyme disease vaccine candidate currently in clinical development, which is currently in Phase 3 human trials. VLA15 is a multivalent protein subunit vaccine that targets the OspA. The vaccine covers the six most common OspA serotypes expressed by the Borrelia burgdorferisensu lato species that are prevalent in North America and Europe. VLA15 has demonstrated a strong immune response and satisfactory safety profile in pre-clinical and clinical studies so far.
References
| Cat. No | Product Name | Species Reactivity | Sample | |
| DEIA2214 | Borrelia burgdorferi IgM ELISA Kit | Human | Serum | Inquiry |
| DEIA1717 | Human Borrelia burgdorferi IgG/IgM ELISA Kit | Human | Serum | Inquiry |
| DEIA1718 | Human Borrelia burgdorferi IgG ELISA Kit | Human | Serum | Inquiry |
| DEIA1975 | Borrelia burgdorferi IgM ELISA Kit | Human | Serum, plasma, cerebrospinal fluid | Inquiry |
| DEIA587 | Human B. Burgdorferi ELISA Kit | Human | Plasma, serum, cerebrospinal fluid | Inquiry |
| DEIA2335 | Human Lyme Disease IgG ELISA Kit | Human | Serum | Inquiry |
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