Background
Lyme disease is the most prevalent tick-borne disease in North America and Europe. The primary causative agent is Borrelia burgdorferi sensu stricto (B. burgdorferi). When being bitten by a black-legged tick (Ixodes scapularis) or western black-legged tick (Ixodes pacificus) with the infection, B. burgdorferi enters the bloodstream and attacks a variety of tissues, including the heart, brain, and joints, causing a persistent infection. Several signs can indicate Lyme illness. The characteristic erythema migrans rash and symptoms similar to the flu can be signs of an early localized infection. Neurological symptoms, including meningitis, facial palsy, neuritis, and Lyme carditis, can emerge months after the infection begins to advance. In late-stage Lyme disease, chronic symptoms include peripheral neuropathy, arthritis, extreme fatigue, and other long-term problems may develop.
Antibiotics are the most effective treatment for Lyme disease. Tetracyclines, β-lactam antibiotics, and macrolides are effective against B. burgdorferi, to varying degrees. However, persistent Lyme disease symptoms can last for years after antibiotic therapy (post-treatment Lyme disease syndrome, or PTLDS), which is why Lyme disease immunization is critical. Borrelia spirochetes feature a variety of surface proteins that are possible vaccine targets and have been the focus of research. In the 1990s, researchers developed two vaccines based on the surface protein OspA, but they were eventually discontinued due to a lack of license and substantial side effects. Subsequently, efforts have shifted towards other surface proteins, with outer surface protein C (OspC) being one of the recent focuses in Lyme disease research and treatment.
OspC plays a critical role during the early stages of mammalian infection by helping the pathogen evade the host's immune surveillance and successfully invade host cells. The clinical potential of OspC in Lyme disease treatment and prevention is gaining increasing attention. OspC exhibits high variability, with sequence differences correlating with changes in tissue invasiveness. Different OspC types may influence disease manifestations and prognosis. Based on this evidence, researchers are exploring strategies for utilizing OspC protein in Lyme disease vaccine development, showing promising clinical potential. Currently, canine subunit vaccines using OspC derivatives as antigens are available on the market, demonstrating good immunogenicity and protective capabilities. However, despite the suitability of OspC's expression pattern for targeting by vaccine antibodies, developing an OspC-based vaccine still faces challenges due to its inherent sequence diversity and immune evasion sites. Expanding the protective scope of OspC to achieve broad protection remains a goal. The exploration of OspC holds promise for advancing Lyme disease vaccines and therapeutic drugs, offering hope for more effective solutions to this global health issue.
Alternative Names
B. burgdorferi OspC
outer surface protein C Lyme disease
OspC Lyme disease
Borrelia burgdorferi OspC
Recombinant OspC
References
Development and optimization of OspC chimeritope vaccinogens for Lyme disease
Vaccine
Authors: Izac, J.R. O'Bier, N.S. Oliver, L.D. Jr. Camire, A.C. Earnhart, C.G. Rhodes, D.V.L. Young, B.F. Parnham, S.R. Davies, C. Marconi, R.T.
Abstract
Experimental Outer surface protein (Osp) C based subunit chimeritope vaccinogens for Lyme disease (LD) were assessed for immunogenicity, structure, ability to elicit antibody (Ab) responses to divergent OspC proteins, and bactericidal activity. Chimeritopes are chimeric epitope based proteins that consist of linear epitopes derived from multiple proteins or multiple variants of a protein. An inherent advantage to chimeritope vaccinogens is that they can be constructed to trigger broadly protective Ab responses. Three OspC chimeritope proteins were comparatively assessed: Chv1, Chv2 and Chv3. The Chv proteins possess the same set of 18 linear epitopes derived from 9 OspC type proteins but differ in the physical ordering of epitopes or by the presence or absence of linkers. All Chv proteins were immunogenic in mice and rats eliciting high titer Ab. Immunoblot and enzyme linked immunosorbent assays demonstrated that the Chv proteins elicit IgG that recognizes a diverse array of OspC type proteins. The panel included OspC proteins produced by N. American and European strains of the LD spirochetes. Rat anti-Chv antisera uniformly labeled intact, non-permeabilized Borreliella burgdorferi demonstrating that vaccinal Ab can bind to targets that are naturally presented on the spirochete cell surface. Vaccinal Ab also displayed potent complement dependent-Ab mediated killing activity. This study highlights the ability of OspC chimeritopes to serve as vaccinogens that trigger potentially broadly protective Ab responses. In addition to the current use of an OspC chimeritope in a canine LD vaccine, chimeritopes can serve as key components of human LD subunit vaccines.
Current Treatment Approaches to Eliminate Borrelia burgdorferi and Potential Strategies to Alleviate Persistent Lyme Disease Symptoms
Preprints
Authors: Zafar, K., Azuama, O., Parveen, N.
Abstract
Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.
COA
Publication 
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