RARE DISEASE
Lyme disease
Lyme disease
Lyme disease
Synonyms: Lyme borreliosis
Synonyms: Lyme borreliosis
Synonyms: Lyme borreliosis
Drug discovery
2,204
papers
On emerging therapies
Overview
Lyme disease, caused by Borrelia burgdorferi and transmitted via blacklegged ticks, is the most common vector-borne illness in the U.S. Early localized infection often presents with erythema migrans rash, fever, and fatigue. Untreated cases may progress to disseminated arthritis, neurologic deficits, or cardiac complications. Diagnosis relies on clinical suspicion, exposure history, and serologic testing, while treatment focuses on prompt antibiotic therapy to prevent chronic sequelae [1][4][5][19].
Population
Bimodal age distribution (peaks at 5–14 and 45–64 years), with slight male predominance [1][6][18].
Higher incidence in White individuals, but racial/ethnic minorities face delayed diagnoses and more severe manifestations [2][12].
Endemic in Northeast, mid-Atlantic, and upper Midwest U.S. regions [5][10].
Therapies
First-line: Oral doxycycline (10–21 days) for early/localized disease; IV ceftriaxone for neurologic/cardiac involvement [3][7][11].
Post-treatment Lyme disease (PTLDS) management prioritizes symptom relief, not prolonged antibiotics [13][19][20].
Single-dose doxycycline prophylaxis recommended for high-risk tick bites in endemic areas [7][19].
Categories: rare infectious diseases, rare neurological diseases
Research Papers
2,204 drug discovery papers about Lyme disease, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
2,204 drug discovery papers about Lyme disease, with 1 first-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-30 | Is 28 days of doxycycline still justified for canine Lyme arthropathy? A call for a randomized controlled trial.
Canine Lyme borreliosis is commonly treated with a 28-day course of doxycycline, a regimen based on historical precedent rather than evidence. Most dogs exposed to Borrelia burgdorferi remain clinically normal despite seroconversion; of those that do develop clinical Lyme disease, the most common presentation is acute or recurrent shifting-leg lameness consistent with Lyme arthropathy. This Viewpoint proposes there is clinical equipoise to evaluate shorter durations of 10 days of doxycycline in dogs with uncomplicated Lyme arthropathy and outlines a prospective parallel-group randomized controlled trial to reassess treatment duration. Determining whether a shorter treatment course is clinically effective also has important implications for antimicrobial stewardship by minimizing unnecessary antimicrobial exposure and selection pressures for antimicrobial resistance.
2026-09-29 | Metabolic regulation of the carbonyl stress pathway and methylglyoxal in Lyme disease and relapsing fever spirochetes.
The carbonyl stress pathway in bacteria is mediated by the enigmatic metabolite methylglyoxal and is thought to be activated in response to cellular carbohydrate and phosphate imbalance. Methylglyoxal, produced from dihydroxyacetone phosphate by methylglyoxal synthase, covalently modifies nucleophilic groups of amino acid residues, such as lysine, arginine and cysteine, to yield advanced glycation end products. In this work, we have identified several environmental signals, including glycerol and peptides, which activate carbonyl stress in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi. We establish that methylglyoxal production and protein glycation is dependent on the mgsA gene (bb0364) product and show that this pathway is active in Lyme disease spirochetes, but not relapsing fever Borrelia or in B. mayonii. Furthermore, we have investigated the role of carbonyl stress in the tick-mouse model of Lyme disease and provide evidence that production of methylglyoxal and glycation of proteins is not necessarily lethal, as previously believed, at least in Lyme disease spirochetes. Finally, we show that expression of the B. burgdorferi mgsA and carbonyl stress pathway in the relapsing fever spirochete B. hermsii significantly reduces the peak level of spirochetemia during the relapse phase of murine infection. Together, our results identify a new post-translation modification system in Lyme disease spirochetes that appears to be important in governing the lifestyle of this pathogen and seems to be selected against in spirochetes that reach high numbers in the blood.
2026-09-25 | Equine neuroborreliosis in Scandinavia: cerebrospinal fluid PCR confirmation and successful treatment in a mare.
Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato, is an emerging concern in human medicine, and is a controversial topic in equine medicine. Neuroborreliosis (NB), a neurologic manifestation of LB, remains challenging to diagnose due to nonspecific clinical signs and the lack of definitive diagnostic methods. This report describes the first documented case of equine NB in Scandinavia. An 11-year-old mare presented with progressive weight loss, ataxia, muscle atrophy, and hyperesthesia. Cerebrospinal fluid (CSF) analysis revealed neutrophilic pleocytosis, elevated protein and a positive PCR result for Borrelia spp. The mare showed clinical improvement and long-term recovery following prolonged doxycycline therapy. This case is the first reported case of neuroborreliosis in a horse in Scandinavia and supports the diagnostic relevance of CSF PCR in conjunction with clinical and cytological findings. It also underscores the potential for recovery in equine NB when early antimicrobial treatment is initiated.
2026-09-22 | Mostly getting along -Borrelia burgdorferi and its manipulation of the host immune system.
Lyme disease is caused when mammalian hosts not part of the sylvatic life cycle, including humans, are infected with Borrelia burgdorferi (Bb) following the bite of an Ixodes tick. Ticks and natural mammalian host reservoirs, including rodents, however, are largely disease tolerant, despite Bb establishing persistent infection. We explore the complex and ongoing interplay between Bb and the immune system. We discuss how Bb infection-induced innate responses seem maladapted to this extracellular bacterial infection, perhaps explaining why CD4+ T cells are ineffective contributors to Bb infection control. While B cell responses critically control Bb tissue burden and disease development they cannot clear the infection, showing a bias towards ongoing plasmablast responses and a lack of functional germinal centers. Identifying the mechanisms that hinder effective immune clearance of Bb may lead to new approaches for the treatment of Lyme Disease.
2026-08-13 | Lyme Disease and Wellness Innovation
Lyme disease is a complex, multi-system illness caused primarily by Borrelia burgdorferi and transmitted through the bite of infected ticks.While early-stage Lyme disease may present as an acute infection with recognizable symptoms and is often responsive to timely antibiotic intervention, delayed diagnosis or incomplete treatment can allow the condition to progress into a chronic and debilitating state for a subset of individuals.In these cases, patients may experience persistent and relapsing symptoms that affect neurological, musculoskeletal, cardiovascular, gastrointestinal, and immune systems, significantly impairing quality of life.Conventional medical management of Lyme disease has historically focused on antimicrobial therapy as the primary line of treatment.However, a growing body of clinical and translational research suggests that ongoing symptoms in chronic or post-treatment Lyme disease are not solely attributable to active infection.Instead, they are increasingly understood to involve downstream biological disruptions, including immune system dysregulation, chronic low-grade inflammation, mitochondrial dysfunction, oxidative stress, autonomic imbalance, and alterations in the gut microbiome.These interrelated mechanisms can perpetuate fatigue, pain, cognitive dysfunction, mood disturbances, metabolic instability, and impaired detoxification capacity long after antimicrobial therapy has concluded.This white paper explores Lyme disease through an integrative biomedical and wellness-based lens, emphasizing the importance of addressing both pathogen-related factors and host resilience.It examines how targeted nutritional and botanical interventions specifically the strategic use of vitamins, minerals, antioxidants, and herbal compounds may help modulate inflammatory signaling, support mitochondrial energy production, enhance immune regulation, reduce oxidative burden, and restore gut and barrier integrity.When thoughtfully integrated alongside conventional medical care, these approaches may contribute to improved physiological adaptability, symptom management, and long-term recovery outcomes.By bridging conventional infectious disease management with systems-based nutritional and metabolic support, this paper aims to provide a more comprehensive framework for understanding and supporting individuals affected by Lyme disease.The goal is not to replace standard medical treatment, but to complement it with evidence-informed strategies that address the complex biological terrain underlying chronic symptoms, ultimately promoting greater resilience, functional recovery, and overall wellness.PriMera Scientific Surgical Research and Practice https://primerascientific.com/pssrp Lyme Disease and Wellness Innovation 47
antibodies
2026-05-11 | Tick-Borne Infection as a Precipitant of Guillain-Barré Syndrome: A Case of Lyme Neuroborreliosis.
Overlapping clinical features between Lyme disease and Guillain-Barré Syndrome (GBS) can complicate diagnosis, and a definitive causal relationship has not been established. A 58-year-old woman experiencing unsheltered homelessness was referred to the emergency department by her street medicine physician with progressive symmetric weakness, unilateral facial nerve palsy, dysphagia, and dyspnea following tick bites obtained at her encampment in the woods. Workup showed elevated cerebrospinal fluid (CSF) protein with lymphocytic pleocytosis and positive serum Lyme serology tests, consistent with acute infection with Borrelia burgdorferi. Electromyography (EMG) demonstrated proximal demyelination, raising concern for concurrent GBS. She was treated with intravenous ceftriaxone and intravenous immunoglobulin (IVIG), resulting in gradual neurological improvement. This case underscores that Lyme neuroborreliosis can mimic or precipitate GBS-like neuropathy, and when overlap cannot be excluded, combined antibiotic and immunotherapy may be necessary. Early recognition is crucial to prevent respiratory or cardiac complications from overlapping Lyme and GBS pathology. This case underscores the importance of diagnosing and distinguishing GBS from Lyme neuroborreliosis when features overlap. Recognition of atypical findings, particularly inflammatory cerebrospinal fluid profiles, is essential to guide appropriate combined therapy and optimize neurological outcomes.
2026-04-29 | Heritable immunization of mice against Lyme disease enables ecological disease prevention.
Heritable immunization is a promising approach to controlling infectious diseases by embedding immunity directly into the genomes of wild species that spread human pathogens. Here, we report the genetic engineering of Mus musculus to genomically encode a single-chain antibody against Borrelia burgdorferi, the causative agent of Lyme disease. After optimization of the antibody format, engineered mice stably produce a LA-2 scFv-albumin fusion protein targeting the Borrelia outer surface protein A (OspA) across multiple generations, demonstrating robust heritability and stability of gene expression. Following sequential challenges with infected and uninfected ticks, heterozygous mice exhibit strong resistance to infection, effectively interrupting the Borrelia burgdorferi disease transmission cycle. Having recently established protocols to genetically engineer the white-footed mouse Peromyscus leucopus, a key reservoir of Lyme disease, these findings demonstrate the feasibility of heritable immunization as a potential strategy for mitigating Lyme disease transmission in the environment. Engineered reservoir immunity may offer a promising approach to controlling vector-borne and zoonotic disease.
2026-04-21 | OspA antibodies inhibit the in vitro transmigration of Borrelia burgdorferi.
Antibodies against Outer surface protein A (OspA) block tick-to-mammal transmission of the Lyme disease spirochete, Borrelia burgdorferi. Evidence suggests that antibodies ingested by a tick during a blood meal entrap OspA-expressing B. burgdorferi within the tick midgut and prevent spirochete migration to the salivary gland and host dermis. In this study, we employed a recently described Transwell system to quantitate the impact of OspA antibodies on B. burgdorferi transmigration. We demonstrate that spirochete movement from the lower Transwell chamber to the upper chamber over a 20-h period was reduced by >99% in the presence of the transmission-blocking mouse monoclonal IgG antibody (mAb) LA-2. In the case of LA-2, transmigration inhibition coincided with the formation of large antibody-induced bacterial aggregates in the lower Transwell chamber, as determined by dark field microscopy and flow cytometry. Further examination of a panel of human OspA mAbs of varying affinities and epitope specificities revealed that virtually all could block B. burgdorferi transmigration although most did so in the absence of measurable spirochete agglutination. We propose that transmigration arrest may represent a possible mechanism by which OspA antibodies entrap B. burgdorferi in the tick midgut and limit transmission to mammalian hosts.
2026-04-15 | Autoimmune Epilepsy Temporally Associated With Lyme Disease: A Report of Two Cases.
The relationship between Lyme-associated illness and immune-mediated seizure disorders remains incompletely characterized. Infection-triggered neurologic immune syndromes are well described in some settings, but evidence linking Borrelia burgdorferi to autoimmune epilepsy remains limited and is based primarily on isolated reports. We describe two previously healthy patients, a 25-year-old male and a 14-year-old female, who developed new-onset seizures temporally associated with Lyme-associated illness and the initiation of antimicrobial therapy. Diagnostic evaluation included serologic testing for tick-borne disease performed through outside commercial laboratories and subsequent reference laboratory testing, cerebrospinal fluid (CSF) analysis, neuroimaging, electroencephalography, neural autoantibody testing, quantitative immunoglobulins, IgG subclass testing, and complement studies. In both cases, seizure activity persisted despite multiple antiseizure medications and worsened after initiation of antimicrobial therapy. Laboratory evaluation demonstrated hypogammaglobulinemia with IgG subclass deficiencies and complement abnormalities in both cases. Neural autoantibody testing revealed elevated anti-dopamine receptor D1 antibodies in both patients; the adult patient also had a low-titer serum N-methyl-D-aspartate receptor antibody detected by a cell-based assay. Immunomodulatory therapy with systemic corticosteroids, followed by intravenous immunoglobulin, administered while antimicrobial therapy was continued, was associated with marked seizure reduction and sustained clinical improvement. These cases demonstrate a temporal association between Lyme-associated illness, antimicrobial treatment, infection-associated immune activation, and treatment-refractory seizures. The clinical deterioration observed after initiation of antimicrobial therapy may reflect an inflammatory response associated with microbial die-off, similar to a Jarisch-Herxheimer-type reaction described in spirochetal infections. Although the findings do not establish a causal relationship between Lyme disease and autoimmune epilepsy, they raise the possibility that infection-associated immune dysregulation may contribute to seizure pathogenesis in selected patients. These observations are hypothesis-generating and support maintaining a broad differential diagnosis, including neuroimmune mechanisms, in patients presenting with new-onset seizures in the setting of suspected infectious illness.
2026-03-28 | Characterization of Borrelia-Derived Extracellular Vesicles: Implications for Pathogenesis and Diagnostics.
The cause of chronic neurological effects associated with Lyme disease (LD) remains unclear. We propose that bacterial extracellular vesicles (BEVs) released by Borrelia burgdorferi, the causative agent of LD, exacerbate spirochete-induced damage and serve as a persistent source of antigenic stimulation. We showed that, over a 10-day period, in vitro cultures of B. burgdorferi B31 produced 38,000 BEVs per spirochete with a distinctive double-membrane structure and median diameter of 143.3 nm. BEVs contained known immunogenic and immunomodulatory molecules such as peptidoglycan, p66, flagellar filament protein (FlaB), basic membrane proteins A/B/D, BdrV, GroEL, CRASP-1, ErpA8, glycerophosphodiester phosphodiesterase, p37, OMS28, p13, OspA/B/C, VlsE, and outer membrane glycolipids (e.g., cholesteryl 6-O acyl beta D galactopyranoside). Chromosome-encoded 16S ribosomal RNA and cp32 plasmid-encoded OspE and terminase genes were also detected in the BEVs. Of the 45 Borrelia proteins identified in the urine of a C3H/HeJ murine model of Lyme disease, 14 were associated with BEVs. In human urine samples, 31 of 289 spirochete proteins detected in patients with either acute Lyme disease or persistent borreliosis post-treatment symptoms, including p66 and FlaB, were also BEV-associated. BEV treatment of HMC3 human microglial cells reduced phagocytic activity and triggered aberrant activation of inflammatory and immunometabolic pathways, including upregulation of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and Toll-like receptor 2 (TLR2) gene expression. BEVs also induced NRF2 nuclear translocation. In conclusion, these findings support that BEVs can amplify spirochete-induced damage and act as antigenic debris, driving dampened phagocytic activity and dysregulated inflammation, with implications for diagnostics and therapeutics targeting vesicle-mediated pathology.
vaccines
2026-09-02 | A second yearly booster dose of the VLA15 Lyme borreliosis vaccine candidate in healthy individuals.
Human vaccines against Lyme borreliosis, the most common tick-borne illness in Northern Hemispheric temperate climates, remain unavailable. Previous evaluations demonstrated the safety and immunogenicity of primary and booster dosing with VLA15, an investigational vaccine containing six Borrelia burgdorferi sensu lato outer surface protein A serotypes. In this randomized, observer-blinded, placebo-controlled, phase 2 trial, participants 5 - 65 years of age were randomized 1:1:1 to receive VLA15 at Months (M) 0, 2, and 6; VLA15 at M0 and M6 and placebo at M2; or placebo at each time point. VLA15 and placebo recipients received VLA15 boosters and placebo, respectively, at M18 and M30. Here we report safety and immunogenicity from M19 through M31; earlier data were reported previously. In both VLA15 groups, serotype-specific immunoglobulin G geometric mean titers declined after the M18 booster but remained higher than after primary vaccination. The M30 VLA15 boosters induced robust, anamnestic immune responses across serotypes and age groups that were qualitatively similar to those after the M18 boosters. The M18 and M30 boosters had similar, acceptable tolerability profiles; no safety concerns arose through M31. These results further support the paradigm of VLA15 primary vaccination followed by yearly boosting to optimize potential protection against Lyme borreliosis. ( ClinicalTrials.gov: NCT04801420 ).
2026-08-26 | Lessons Unlearned: The Barriers to Lyme Borreliosis Vaccination and the Risk of Repeating History.
Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first licensed vaccine against Lyme borreliosis. Its withdrawal four years later was not driven by evidence of vaccine failure but by the collapse of public confidence, and regulatory endorsement that any successful vaccine programme requires. The field was without a licensed product for twenty-four years. VLA15 (now designated PF-07307405), a second-generation recombinant outer surface protein A vaccine, is now at regulatory submission following phase 3 results reported in March 2026. We examine the barriers that led to LYMErix's withdrawal, revisit the evidence that generated and sustained the safety controversy and consider whether the conditions now exist for a different outcome. The lessons for a robust post-marketing surveillance programme extend beyond Lyme borreliosis to broader questions about how modern medicine evaluates vaccine risk, interprets safety signals, and communicates under uncertainty.
2026-06-22 | The current landscape and future directions of Lyme disease vaccines.
Lyme disease (LD) represents a significant public health challenge in North America and Eurasia. The persistent increase in its incidence may create an opportunity for vaccines to gain broader acceptance. Recent years have seen notable advances in vaccine development. However, achieving a balance between broad-spectrum protection and durable immunity remains a critical bottleneck. This article is presented as a narrative review that systematically summarizes recent progress in Lyme disease vaccine research worldwide, with particular emphasis on the strengths and limitations of approved and investigational candidates. Unlike existing reviews, this study integrates recent clinical investigations of multivalent vaccine candidates with breakthrough advances across diverse vaccine platforms, yielding a comprehensive and current synthesis. We identify critical challenges in contemporary vaccine development and propose actionable solutions. Our forward-looking perspective centers on a triangular strategy that integrates antigen multivalency, platform personalization, and geographical customization, providing a conceptual framework to guide future LD immunoprophylaxis research.
2026-06-21 | Natural antibodies induced by host gut microbiota modulate tick microbiota, inhibiting Borrelia colonization.
The gut microbiome undergoes natural selection pressure, likely because it can affect infection resistance by stimulating natural antibody (NAb) production, notably against the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal). In our study, we explored whether particular glycans, such as α-Gal, from specific host microbiota components could trigger NAbs that, once ingested by Ixodes ricinus ticks during the blood meal, are capable of cross-reacting with bacterial strains in the tick microbiota that share these glycans. Such interactions might alter the tick microbiota and reduce Borrelia afzelii colonization in ticks. When mice were orally administered various Escherichia coli strains, it triggered the stimulation of NAbs and resulted in strain-specific alterations in the tick microbiota. These changes effectively decreased Borrelia colonization in the tick vector. Additionally, vaccination with the glycan α-Gal induced notable shifts in the tick microbiota and similarly reduced Borrelia colonization. Reduced Borrelia colonization was associated with shifts in bacterial diversity, abundance, and microbial network properties. The study provides evidence that natural mechanisms, such as the production of NAb in response to the host gut microbiome, can modulate the microbiota of disease vectors and reduce pathogen colonization within the vector. These findings offer new insights into potential strategies for reducing the transmission of vector-borne diseases through modulation of the host gut microbiome.
2026-05-17 | Developing a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rationale adjuvant selection.
Rational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacterium Borrelia burgdorferi (Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no approved human vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S, with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy after Bb infection. We identified Alum-CpG and Alum-αGal to elicit the highest titers of CspZ-YAC187S-dependent protective antibodies and robust levels of protection, but through distinct mechanisms of immunomodulation. We demonstrated that immunization with Alum-CpG formulated CspZ-YAC187S provided up to nine months of protective bactericidal antibody titers, as well as recall-memory response to prevent LD after natural infection. Immunity was linked to elevated levels of IgG1 memory cells in the vaccine-triggered immune responses. This work thus identified a durable, memory immunity-driven LD vaccine, ultimately paving the road to understand the mechanisms of rationale adjuvant selection for vaccine development.
proteins
2026-07-15 | Single-step immunoblot tests with recombinant protein antigens for detecting IgG and IgM antibodies in Lyme disease.
Serodiagnosis is important in Lyme disease (LD). Until recently, this commonly required two separate tests termed the standard two-tier tests (STTTs). One-step immunoblot (IB) tests utilizing recombinant protein targets from multiple Borrelia species and strains that may simplify the serodiagnosis of LD are now described. Specificity of the IB tests was established with 425 sera from healthy persons and 387 sera from persons with potentially confounding infections and medical conditions. Test sensitivities were determined with (i) 90 sera from patients with different stages of LD from the US Centers for Disease Control and Prevention (CDC), and (ii) 290 prospectively banked sera from patients with acute-stage LD from the Bay Area Lyme Foundation's Lyme Disease Biobank (BALDB). The IgG IB test was more sensitive than a US Food and Drug Administration (FDA)-cleared STTT for detecting IgG antibodies in stage 1 LD sera from the CDC's test panel (P = 0.002). The diagnostic performance of the IgG and IgM IB tests demonstrated significantly greater overall sensitivity than the comparable FDA-cleared STTTs for detecting IgG and/or IgM antibodies in the 290 BALDB sera (P = 0.00004). The IgG IB test was also more sensitive than the IgG STTT for detecting IgG antibodies in the 290 BALDB sera (P < 0.000001). The IgG and IgM IB tests were additionally more sensitive than IgG and IgM STTTs for detecting IgG and/or IgM antibodies in BALDB sera from 189 patients with erythema migrans (P = 0.03). The IB tests described here form the basis for one-step IgG and IgM IB tests, termed iDart IgG and IgM IB tests, cleared by the FDA for LD diagnosis.IMPORTANCEThe immunoblot (IB) tests described here are one-step tests that separately detect IgG and IgM antibodies for the serological diagnosis of Lyme disease in the United States. The IB tests are more sensitive than a common standard two-tier test for detecting antibodies in early-stage Lyme disease. This can assist in the diagnosis of Lyme disease when antibodies have not yet reached their maximum concentration in patient sera.
2026-05-18 | A lipid-binding protein in black-legged tick saliva selectively recognizes Borrelia burgdorferi lipids.
A proteomic analysis of Ixodes scapularis nymph saliva identified 252 proteins, including six tubular lipid-binding proteins (TULIPs). Comparing nymphs fed on mice that were uninfected or infected with Borrelia burgdorferi, twelve salivary proteins showed significant differences in the amounts detected, including XP_040079658.2, which we refer to as TULIP2. Considering the known immunity-related functions of some TULIPs, we expressed and purified TULIP2 from Escherichia coli and analyzed its interaction with B. burgdorferi lipids. The purification of TULIP2 from E. coli presented many obstacles, due to insolubility, which is consistent with previous reports from studies of other TULIP family members. The binding results showed specificity for B. burgdorferi lipids, with evidence for cholesteryl β-galactoside as a major binding target. Molecular modeling of TULIP2 did not show any strong lipid binding sites. We used molecular dynamics simulation of TULIP2 to explore its conformational landscape by thermal unfolding. The earliest unfolding intermediate opened a hydrophobic pocket to which cholesteryl β-galactoside was predicted to bind strongly. We propose that a specific lipid bilayer interaction with TULIP2 triggers the opening of the ligand-binding site.
2026-05-05 | Borrelia burgdorferi sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System.
Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) through Ixodes tick bites, presents diverse clinical manifestations and may lead to persistent symptoms. This review summarizes current knowledge on the pathogen-host interactions and immune responses. Early infection can be influenced by tick saliva, which suppresses local host defense and promotes spirochete survival, and by pattern recognition receptors activating proinflammatory cascades. Bbsl employs a variety of immune evasion strategies, notably impairing antigen presentation-through disruption of MHC II and IFN-γ pathways-and continuously varying surface antigens to hinder long-lasting antibody formation. Autophagy plays a central role in modulating inflammation and T helper 17 adaptive immune responses, representing an underappreciated mechanism potentially influencing disease outcome. Adaptive immunity in LB is characterized by robust but often dysregulated humoral and cellular responses, with transient germinal centers and enduring IgM production contributing to incomplete pathogen clearance. Persistent immune defects include impaired long-term B cell memory, suppressed T cell activation, and ongoing immunosuppression after pathogen clearance. Similar patterns are observed in other postinfectious fatigue syndromes. Despite advances, gaps remain in understanding mechanisms of Bbsl persistence and the immunopathology underlying chronic disease, challenging diagnosis and therapy. Emerging molecular and cellular approaches offer new avenues to address immunity, diagnostics, and prevention. A multidisciplinary effort will be needed to improve long-term patient outcomes in the evolving epidemiology of LB.
2026-03-27 | Innate Immune Evasion of Lyme Disease Pathogen Drives Alzheimer-Like Pathology.
The amyloid β (Aβ) peptide is the main component of amyloid plaques in Alzheimer's disease (AD). Growing evidence has pointed to a role for Aβ as an antimicrobial peptide (AMP). However, the interactions of Aβ with neurotropic pathogens and host evasion strategies have remained largely unexplored. Using quantitative proteomic analysis of patient cerebrospinal fluid (CSF), advanced biochemical methods, and four different 3D brain models, ranging from blood-brain barrier (BBB) microfluidic systems to 3D neurovascular networks, we show that Lyme neuroborreliosis (LNB) Borrelia spp. induce molecular and immunological alterations in the central nervous system (CNS) that resemble key pathological features of AD. These include upregulation of the complement cascade and a decrease in CSF Aβ levels. By assessing the antimicrobial action of Aβ against Borrelia spp., we demonstrate that Aβ acts as a pre-opsonin by promoting complement activation on microbial surfaces. We also show that LNB Borrelia spp. exhibit unique survival strategies that reduce Aβ binding and block oligomerization, while halting complement attack by recruiting complement regulator factor H. This facilitates bacterial adhesion to the BBB, and modulation of glial and cytokine responses, fostering CNS invasion. Our findings reveal a previously unrecognized mechanism of bacterial immune escape spanning the entire invasion pathway from the BBB to neuronal compartments, demonstrating that LNB Borrelia spp. evade Aβ-mediated antimicrobial action by interfering with opsonization and oligomerization of the peptide. Collectively, these findings provide a direct mechanistic link between pathogen immune evasion, Aβ dynamics, and neuroinflammatory cascades, advancing our understanding of infection-induced neuropathology, offering insights into novel potential therapeutic targets for AD and neuroborreliosis.
2026-02-25 | EXPRESS: A Comprehensive Review of Lyme disease in Latin America.
Lyme disease (LD) is caused by a bacterial genospecies complex named Borrelia burgdorferi sensu lato (s.l.), which includes B. burgdorferi sensu stricto (B.b.s.s). Originally described in North America, LD has also been described in other parts of the Northern Hemisphere, and in Eurasia. Different B.b.s.l. species, transmitted through geographically diverse tick vectors, are associated with different clinical presentations of the disease. In recent years, the incidence and the endemic range of LD have steadily expanded to include areas of the world with tropical climate, including Latin American countries.Challenges in serological diagnosis. Inconsistent confirmatory results, despite clinical diagnosis, could be explained by antigenic differences between these new species in these countries, with American strains used in the elaboration of commercial tests. This could explain indeterminate Western blots and polymerase chain reactions in detecting suspected LD cases.Novel Borrelia taxons may impact the reservoir host spectrum, including mammals, birds, and other animals. Different species of Ixodes ticks are found in Latin America, where I. scapularis is absent, and they could serve as vectors. New genospecies of B.b.s.l. and the scarce information about its pathogenicity, reservoirs and vectors, highlights the importance of further studies tp elucidate their genetic differences in the context of the development of innovative diagnostic and clinical approaches.Knowledge gaps and the need for prospective and rigorous studies, to determine the presence, or not, of LD in this region, warrant call for research providing new insights into the basic biology and epidemiology, and clinical manifestations in this region.
other
2026-07-28 | Prevalence and Associated Factors of Borrelia burgdorferi Sensu Lato Exposure in Humans and Infection in Questing Ixodes Ticks in China: A Systematic Review and Meta-Analysis.
Lyme borreliosis has been reported across China, but data on Borrelia burgdorferi sensu lato exposure in humans and infection in questing Ixodes ticks remains fragmented and heterogeneous. This systematic review and meta-analysis aimed to estimate the pooled seroprevalence of B. burgdorferi sensu lato exposure in humans and infection prevalence in questing or unfed Ixodes ticks in China and to explore potential sources of heterogeneity. Six English- and Chinese-language databases were searched from inception to 10 September 2025. Eligible cross-sectional studies reported both the number examined and the number positive, with a minimum sample size of 30. Human analyses were restricted to serological evidence, whereas tick analyses included questing or unfed Ixodes ticks collected from vegetation or the environment. Random-effects models, subgroup analyses, and univariate random-effects meta-regression were applied. A total of 186 studies were included, of which 167 reported human data, 22 reported PCR-based data from questing Ixodes ticks, and 3 reported both human and tick data. The pooled human seroprevalence was 7% (95% CI: 6-8%), and the pooled PCR-confirmed infection prevalence in questing Ixodes ticks was 20% (95% CI: 10-32%). Substantial heterogeneity was observed in both analyses. For questing Ixodes ticks, infection prevalence showed marked geographical heterogeneity, with the highest pooled estimate observed in Northeastern China. In univariate meta-regression, Northern China showed a significantly lower estimate than Northeastern China, whereas sampling year, reported Borrelia genospecies, and Ixodes species were not significantly associated with pooled prevalence. Leave-one-out analyses indicated that the pooled estimates were not driven by any single study. These findings demonstrate that human exposure and environmental circulation of B. burgdorferi sensu lato have been documented across multiple regions of China but remain highly heterogeneous.
2026-05-24 | Evaluation of EcoCRM, virus-like particles, and mRNA as vaccine platforms against Borrelia burgdorferi.
Lyme disease (LD) is the most prevalent vector-borne disease in the United States, impacting ∼476,000 individuals annually with increasing incidence. Prevention relies on personal protective measures such as insecticides and tick checks, underscoring the need for new preventatives such as vaccines. In this work, the importance of vaccine platform in LD vaccine development efforts was evaluated using non-lipidated OspA as model antigen. Recombinant OspA conjugated to CRM197 (EcoCRM OspA), a virus-like particle vaccine utilizing SpyTag and SpyCatcher (OspA-SpyVLP), and an mRNA-based vaccine construct (OspA mRNA) were evaluated and compared in C3H mice using the needle injection challenge model. To determine immunogenicity, anti-OspA and anti-B. burgdorferi antibodies were quantified via ELISA and further assessed by measuring IgG subclass, antibody avidity, and presence of antibody secreting cells. All vaccine formulations were immunogenic and led to the release of similar levels of antigen-specific IgG in serum during the duration of the experiment. However, there were significant differences around two week post-boost in the presence of antibody secreting cells, ratio of IgG1/IgG2 subclasses, and antibody avidity between platforms. Protection was measured using PCR and darkfield microscopy to determine organ positivity post-challenge. Vaccination with recombinant non-lipidated OspA and OspA-SpyVLP significantly reduced the number of positive organs compared to the PBS challenged control group. Lastly, in vitro borreliacidal activity was quantified via darkfield microscopy and the highest borreliacidal activity was observed using OspA-SpyVLP sera, with titers 16-fold higher than recombinant OspA. Altogether, these data indicated that selection of vaccine platform/formulation influenced the immunogenicity and efficacy of OspA-based LD vaccines and should be considered during development.
2026-02-19 | Non-invasive ovulation tracking enables genetic engineering in wild rodents.
Many non-model rodent species are inaccessible to genetic engineering due to our limited understanding of their reproductive biology. Here, we present a low-cost, camera-based estrous-tracking technology that enables transgenesis in the white-footed mouse Peromyscus leucopus, a key reservoir for Lyme disease. We demonstrate the efficient generation of pregnant and pseudopregnant mice via timed ovulation, provide protocols for embryo generation, cultivation, microinjection, and transplantation as well as an accurate developmental timeline, and report the first engineered Peromyscus. The same technology successfully tracked conserved estrous-linked cycling behavior in other rodents, including hamsters. Finally, estrous tracking differentiated reproductively healthy, geriatric female Peromyscus from those with declining fertility based solely on their activity, providing a non-invasive method for studying reproductive senescence. Collectively, these tools represent a critical resource for engineering non-model rodents, advance the long-lived Peromyscus as a model organism, and will prove essential to heritably immunizing wild rodent populations against Lyme disease.
2026-01-01 | P-1485. Safety and Immunogenicity of mRNA-1982 and mRNA-1975, mRNA Vaccine Candidates for Prevention of Lyme Disease in Healthy Adults: Interim Results of a Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Trial
Abstract Background The incidence of Lyme disease, caused by infection with Borrelia bacteria, continues to rise globally. Previously developed Lyme disease vaccines based on Borrelia OspA antigens elicited antibody responses that correlated with protection; however, no Lyme disease vaccine is currently available for use in humans. Two investigational mRNA vaccines encoding OspA antigens and formulated in a lipid nanoparticle are in development: a monovalent vaccine (mRNA-1982) that covers serotype 1, and a heptavalent vaccine (mRNA-1975) that covers serotypes 1-7. Methods This ongoing Phase 1/2, randomized, observer-blind, placebo-controlled dose-ranging trial in healthy adults 18-70 years of age evaluated the safety and immunogenicity of mRNA-1982 and mRNA-1975 at up to 4 dose levels administered as a 3-injection series at 0, 2, and 6 months (NCT05975099). An interim analysis was conducted with follow-up through 28 days after the 3rd injection for safety and reactogenicity evaluation. Immunogenicity was evaluated by serotype-specific anti-OspA IgG binding antibody responses and by levels of LA-2 equivalent antibody (serotype 1 only). Results At the interim analysis, 745 of 806 enrolled participants completed the 3-injection study vaccine series. Approximately 1% of enrolled participants were seropositive at baseline for prior Borrelia infection. Both mRNA-1982 and mRNA-1975 elicited predominantly mild to moderate reactogenicity that was dose-dependent and increased with each successive injection, with no safety concerns identified. Serotype-specific anti-OspA IgG binding antibody geometric mean-fold rise from baseline and proportions of participants with high levels of LA-2 equivalent antibody responses (≥75% and ≥90% LA-2 inhibition) increased in a dose-dependent manner and with each successive injection across the vaccine groups, compared with no increase in the placebo group. Conclusion Interim data from this ongoing Phase 1/2 trial show that both mRNA-1982 and mRNA-1975 are generally safe and elicit dose-dependent reactogenicity and immunogenicity that increased with each of 3 successive injections. These data will inform the product(s), regimen(s) and dose range(s) to be evaluated in future clinical trials. Disclosures Nina H. Lin, MD, Moderna, Inc: Stocks/Bonds (Public Company) Christina Dold, PhD, Moderna: Stocks/Bonds (Public Company) Meredith Finn, PhD, Moderna: Stocks/Bonds (Public Company) Jacqueline Dooley, BA, Moderna: Stocks/Bonds (Public Company) Rujun Teng, MS, Moderna Inc.: Advisor/Consultant Emma Viscidi, PhD, MHS, ModernaTX: Employee|ModernaTX: Stocks/Bonds (Public Company) Anthony Rizk, PharmD, MBA, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Haixing Wang, PhD, Moderna, Inc.: Stocks/Bonds (Public Company) Doran Fink, MD, PhD, ModernaTX, Inc.: Employee|ModernaTX, Inc.: Stocks/Bonds (Public Company)
2025-12-05 | Polyvalent mRNA vaccine targeting outer surface protein C affords multi-strain protection against Lyme disease.
There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, Borrelia burgdorferi, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.
small molecules
2026-09-30 | Is 28 days of doxycycline still justified for canine Lyme arthropathy? A call for a randomized controlled trial.
Canine Lyme borreliosis is commonly treated with a 28-day course of doxycycline, a regimen based on historical precedent rather than evidence. Most dogs exposed to Borrelia burgdorferi remain clinically normal despite seroconversion; of those that do develop clinical Lyme disease, the most common presentation is acute or recurrent shifting-leg lameness consistent with Lyme arthropathy. This Viewpoint proposes there is clinical equipoise to evaluate shorter durations of 10 days of doxycycline in dogs with uncomplicated Lyme arthropathy and outlines a prospective parallel-group randomized controlled trial to reassess treatment duration. Determining whether a shorter treatment course is clinically effective also has important implications for antimicrobial stewardship by minimizing unnecessary antimicrobial exposure and selection pressures for antimicrobial resistance.
2026-09-29 | Metabolic regulation of the carbonyl stress pathway and methylglyoxal in Lyme disease and relapsing fever spirochetes.
The carbonyl stress pathway in bacteria is mediated by the enigmatic metabolite methylglyoxal and is thought to be activated in response to cellular carbohydrate and phosphate imbalance. Methylglyoxal, produced from dihydroxyacetone phosphate by methylglyoxal synthase, covalently modifies nucleophilic groups of amino acid residues, such as lysine, arginine and cysteine, to yield advanced glycation end products. In this work, we have identified several environmental signals, including glycerol and peptides, which activate carbonyl stress in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi. We establish that methylglyoxal production and protein glycation is dependent on the mgsA gene (bb0364) product and show that this pathway is active in Lyme disease spirochetes, but not relapsing fever Borrelia or in B. mayonii. Furthermore, we have investigated the role of carbonyl stress in the tick-mouse model of Lyme disease and provide evidence that production of methylglyoxal and glycation of proteins is not necessarily lethal, as previously believed, at least in Lyme disease spirochetes. Finally, we show that expression of the B. burgdorferi mgsA and carbonyl stress pathway in the relapsing fever spirochete B. hermsii significantly reduces the peak level of spirochetemia during the relapse phase of murine infection. Together, our results identify a new post-translation modification system in Lyme disease spirochetes that appears to be important in governing the lifestyle of this pathogen and seems to be selected against in spirochetes that reach high numbers in the blood.
2026-09-25 | Equine neuroborreliosis in Scandinavia: cerebrospinal fluid PCR confirmation and successful treatment in a mare.
Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato, is an emerging concern in human medicine, and is a controversial topic in equine medicine. Neuroborreliosis (NB), a neurologic manifestation of LB, remains challenging to diagnose due to nonspecific clinical signs and the lack of definitive diagnostic methods. This report describes the first documented case of equine NB in Scandinavia. An 11-year-old mare presented with progressive weight loss, ataxia, muscle atrophy, and hyperesthesia. Cerebrospinal fluid (CSF) analysis revealed neutrophilic pleocytosis, elevated protein and a positive PCR result for Borrelia spp. The mare showed clinical improvement and long-term recovery following prolonged doxycycline therapy. This case is the first reported case of neuroborreliosis in a horse in Scandinavia and supports the diagnostic relevance of CSF PCR in conjunction with clinical and cytological findings. It also underscores the potential for recovery in equine NB when early antimicrobial treatment is initiated.
2026-09-22 | Mostly getting along -Borrelia burgdorferi and its manipulation of the host immune system.
Lyme disease is caused when mammalian hosts not part of the sylvatic life cycle, including humans, are infected with Borrelia burgdorferi (Bb) following the bite of an Ixodes tick. Ticks and natural mammalian host reservoirs, including rodents, however, are largely disease tolerant, despite Bb establishing persistent infection. We explore the complex and ongoing interplay between Bb and the immune system. We discuss how Bb infection-induced innate responses seem maladapted to this extracellular bacterial infection, perhaps explaining why CD4+ T cells are ineffective contributors to Bb infection control. While B cell responses critically control Bb tissue burden and disease development they cannot clear the infection, showing a bias towards ongoing plasmablast responses and a lack of functional germinal centers. Identifying the mechanisms that hinder effective immune clearance of Bb may lead to new approaches for the treatment of Lyme Disease.
2026-08-13 | Lyme Disease and Wellness Innovation
Lyme disease is a complex, multi-system illness caused primarily by Borrelia burgdorferi and transmitted through the bite of infected ticks.While early-stage Lyme disease may present as an acute infection with recognizable symptoms and is often responsive to timely antibiotic intervention, delayed diagnosis or incomplete treatment can allow the condition to progress into a chronic and debilitating state for a subset of individuals.In these cases, patients may experience persistent and relapsing symptoms that affect neurological, musculoskeletal, cardiovascular, gastrointestinal, and immune systems, significantly impairing quality of life.Conventional medical management of Lyme disease has historically focused on antimicrobial therapy as the primary line of treatment.However, a growing body of clinical and translational research suggests that ongoing symptoms in chronic or post-treatment Lyme disease are not solely attributable to active infection.Instead, they are increasingly understood to involve downstream biological disruptions, including immune system dysregulation, chronic low-grade inflammation, mitochondrial dysfunction, oxidative stress, autonomic imbalance, and alterations in the gut microbiome.These interrelated mechanisms can perpetuate fatigue, pain, cognitive dysfunction, mood disturbances, metabolic instability, and impaired detoxification capacity long after antimicrobial therapy has concluded.This white paper explores Lyme disease through an integrative biomedical and wellness-based lens, emphasizing the importance of addressing both pathogen-related factors and host resilience.It examines how targeted nutritional and botanical interventions specifically the strategic use of vitamins, minerals, antioxidants, and herbal compounds may help modulate inflammatory signaling, support mitochondrial energy production, enhance immune regulation, reduce oxidative burden, and restore gut and barrier integrity.When thoughtfully integrated alongside conventional medical care, these approaches may contribute to improved physiological adaptability, symptom management, and long-term recovery outcomes.By bridging conventional infectious disease management with systems-based nutritional and metabolic support, this paper aims to provide a more comprehensive framework for understanding and supporting individuals affected by Lyme disease.The goal is not to replace standard medical treatment, but to complement it with evidence-informed strategies that address the complex biological terrain underlying chronic symptoms, ultimately promoting greater resilience, functional recovery, and overall wellness.PriMera Scientific Surgical Research and Practice https://primerascientific.com/pssrp Lyme Disease and Wellness Innovation 47
antibodies
2026-05-11 | Tick-Borne Infection as a Precipitant of Guillain-Barré Syndrome: A Case of Lyme Neuroborreliosis.
Overlapping clinical features between Lyme disease and Guillain-Barré Syndrome (GBS) can complicate diagnosis, and a definitive causal relationship has not been established. A 58-year-old woman experiencing unsheltered homelessness was referred to the emergency department by her street medicine physician with progressive symmetric weakness, unilateral facial nerve palsy, dysphagia, and dyspnea following tick bites obtained at her encampment in the woods. Workup showed elevated cerebrospinal fluid (CSF) protein with lymphocytic pleocytosis and positive serum Lyme serology tests, consistent with acute infection with Borrelia burgdorferi. Electromyography (EMG) demonstrated proximal demyelination, raising concern for concurrent GBS. She was treated with intravenous ceftriaxone and intravenous immunoglobulin (IVIG), resulting in gradual neurological improvement. This case underscores that Lyme neuroborreliosis can mimic or precipitate GBS-like neuropathy, and when overlap cannot be excluded, combined antibiotic and immunotherapy may be necessary. Early recognition is crucial to prevent respiratory or cardiac complications from overlapping Lyme and GBS pathology. This case underscores the importance of diagnosing and distinguishing GBS from Lyme neuroborreliosis when features overlap. Recognition of atypical findings, particularly inflammatory cerebrospinal fluid profiles, is essential to guide appropriate combined therapy and optimize neurological outcomes.
2026-04-29 | Heritable immunization of mice against Lyme disease enables ecological disease prevention.
Heritable immunization is a promising approach to controlling infectious diseases by embedding immunity directly into the genomes of wild species that spread human pathogens. Here, we report the genetic engineering of Mus musculus to genomically encode a single-chain antibody against Borrelia burgdorferi, the causative agent of Lyme disease. After optimization of the antibody format, engineered mice stably produce a LA-2 scFv-albumin fusion protein targeting the Borrelia outer surface protein A (OspA) across multiple generations, demonstrating robust heritability and stability of gene expression. Following sequential challenges with infected and uninfected ticks, heterozygous mice exhibit strong resistance to infection, effectively interrupting the Borrelia burgdorferi disease transmission cycle. Having recently established protocols to genetically engineer the white-footed mouse Peromyscus leucopus, a key reservoir of Lyme disease, these findings demonstrate the feasibility of heritable immunization as a potential strategy for mitigating Lyme disease transmission in the environment. Engineered reservoir immunity may offer a promising approach to controlling vector-borne and zoonotic disease.
2026-04-21 | OspA antibodies inhibit the in vitro transmigration of Borrelia burgdorferi.
Antibodies against Outer surface protein A (OspA) block tick-to-mammal transmission of the Lyme disease spirochete, Borrelia burgdorferi. Evidence suggests that antibodies ingested by a tick during a blood meal entrap OspA-expressing B. burgdorferi within the tick midgut and prevent spirochete migration to the salivary gland and host dermis. In this study, we employed a recently described Transwell system to quantitate the impact of OspA antibodies on B. burgdorferi transmigration. We demonstrate that spirochete movement from the lower Transwell chamber to the upper chamber over a 20-h period was reduced by >99% in the presence of the transmission-blocking mouse monoclonal IgG antibody (mAb) LA-2. In the case of LA-2, transmigration inhibition coincided with the formation of large antibody-induced bacterial aggregates in the lower Transwell chamber, as determined by dark field microscopy and flow cytometry. Further examination of a panel of human OspA mAbs of varying affinities and epitope specificities revealed that virtually all could block B. burgdorferi transmigration although most did so in the absence of measurable spirochete agglutination. We propose that transmigration arrest may represent a possible mechanism by which OspA antibodies entrap B. burgdorferi in the tick midgut and limit transmission to mammalian hosts.
2026-04-15 | Autoimmune Epilepsy Temporally Associated With Lyme Disease: A Report of Two Cases.
The relationship between Lyme-associated illness and immune-mediated seizure disorders remains incompletely characterized. Infection-triggered neurologic immune syndromes are well described in some settings, but evidence linking Borrelia burgdorferi to autoimmune epilepsy remains limited and is based primarily on isolated reports. We describe two previously healthy patients, a 25-year-old male and a 14-year-old female, who developed new-onset seizures temporally associated with Lyme-associated illness and the initiation of antimicrobial therapy. Diagnostic evaluation included serologic testing for tick-borne disease performed through outside commercial laboratories and subsequent reference laboratory testing, cerebrospinal fluid (CSF) analysis, neuroimaging, electroencephalography, neural autoantibody testing, quantitative immunoglobulins, IgG subclass testing, and complement studies. In both cases, seizure activity persisted despite multiple antiseizure medications and worsened after initiation of antimicrobial therapy. Laboratory evaluation demonstrated hypogammaglobulinemia with IgG subclass deficiencies and complement abnormalities in both cases. Neural autoantibody testing revealed elevated anti-dopamine receptor D1 antibodies in both patients; the adult patient also had a low-titer serum N-methyl-D-aspartate receptor antibody detected by a cell-based assay. Immunomodulatory therapy with systemic corticosteroids, followed by intravenous immunoglobulin, administered while antimicrobial therapy was continued, was associated with marked seizure reduction and sustained clinical improvement. These cases demonstrate a temporal association between Lyme-associated illness, antimicrobial treatment, infection-associated immune activation, and treatment-refractory seizures. The clinical deterioration observed after initiation of antimicrobial therapy may reflect an inflammatory response associated with microbial die-off, similar to a Jarisch-Herxheimer-type reaction described in spirochetal infections. Although the findings do not establish a causal relationship between Lyme disease and autoimmune epilepsy, they raise the possibility that infection-associated immune dysregulation may contribute to seizure pathogenesis in selected patients. These observations are hypothesis-generating and support maintaining a broad differential diagnosis, including neuroimmune mechanisms, in patients presenting with new-onset seizures in the setting of suspected infectious illness.
2026-03-28 | Characterization of Borrelia-Derived Extracellular Vesicles: Implications for Pathogenesis and Diagnostics.
The cause of chronic neurological effects associated with Lyme disease (LD) remains unclear. We propose that bacterial extracellular vesicles (BEVs) released by Borrelia burgdorferi, the causative agent of LD, exacerbate spirochete-induced damage and serve as a persistent source of antigenic stimulation. We showed that, over a 10-day period, in vitro cultures of B. burgdorferi B31 produced 38,000 BEVs per spirochete with a distinctive double-membrane structure and median diameter of 143.3 nm. BEVs contained known immunogenic and immunomodulatory molecules such as peptidoglycan, p66, flagellar filament protein (FlaB), basic membrane proteins A/B/D, BdrV, GroEL, CRASP-1, ErpA8, glycerophosphodiester phosphodiesterase, p37, OMS28, p13, OspA/B/C, VlsE, and outer membrane glycolipids (e.g., cholesteryl 6-O acyl beta D galactopyranoside). Chromosome-encoded 16S ribosomal RNA and cp32 plasmid-encoded OspE and terminase genes were also detected in the BEVs. Of the 45 Borrelia proteins identified in the urine of a C3H/HeJ murine model of Lyme disease, 14 were associated with BEVs. In human urine samples, 31 of 289 spirochete proteins detected in patients with either acute Lyme disease or persistent borreliosis post-treatment symptoms, including p66 and FlaB, were also BEV-associated. BEV treatment of HMC3 human microglial cells reduced phagocytic activity and triggered aberrant activation of inflammatory and immunometabolic pathways, including upregulation of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and Toll-like receptor 2 (TLR2) gene expression. BEVs also induced NRF2 nuclear translocation. In conclusion, these findings support that BEVs can amplify spirochete-induced damage and act as antigenic debris, driving dampened phagocytic activity and dysregulated inflammation, with implications for diagnostics and therapeutics targeting vesicle-mediated pathology.
vaccines
2026-09-02 | A second yearly booster dose of the VLA15 Lyme borreliosis vaccine candidate in healthy individuals.
Human vaccines against Lyme borreliosis, the most common tick-borne illness in Northern Hemispheric temperate climates, remain unavailable. Previous evaluations demonstrated the safety and immunogenicity of primary and booster dosing with VLA15, an investigational vaccine containing six Borrelia burgdorferi sensu lato outer surface protein A serotypes. In this randomized, observer-blinded, placebo-controlled, phase 2 trial, participants 5 - 65 years of age were randomized 1:1:1 to receive VLA15 at Months (M) 0, 2, and 6; VLA15 at M0 and M6 and placebo at M2; or placebo at each time point. VLA15 and placebo recipients received VLA15 boosters and placebo, respectively, at M18 and M30. Here we report safety and immunogenicity from M19 through M31; earlier data were reported previously. In both VLA15 groups, serotype-specific immunoglobulin G geometric mean titers declined after the M18 booster but remained higher than after primary vaccination. The M30 VLA15 boosters induced robust, anamnestic immune responses across serotypes and age groups that were qualitatively similar to those after the M18 boosters. The M18 and M30 boosters had similar, acceptable tolerability profiles; no safety concerns arose through M31. These results further support the paradigm of VLA15 primary vaccination followed by yearly boosting to optimize potential protection against Lyme borreliosis. ( ClinicalTrials.gov: NCT04801420 ).
2026-08-26 | Lessons Unlearned: The Barriers to Lyme Borreliosis Vaccination and the Risk of Repeating History.
Lyme borreliosis is the most common vector-borne disease in the temperate Northern Hemisphere, with approximately 476,000 diagnoses annually in the United States and over 130,000 reported cases across Europe each year, figures that substantially underestimate true incidence. In 1998, LYMErix became the first licensed vaccine against Lyme borreliosis. Its withdrawal four years later was not driven by evidence of vaccine failure but by the collapse of public confidence, and regulatory endorsement that any successful vaccine programme requires. The field was without a licensed product for twenty-four years. VLA15 (now designated PF-07307405), a second-generation recombinant outer surface protein A vaccine, is now at regulatory submission following phase 3 results reported in March 2026. We examine the barriers that led to LYMErix's withdrawal, revisit the evidence that generated and sustained the safety controversy and consider whether the conditions now exist for a different outcome. The lessons for a robust post-marketing surveillance programme extend beyond Lyme borreliosis to broader questions about how modern medicine evaluates vaccine risk, interprets safety signals, and communicates under uncertainty.
2026-06-22 | The current landscape and future directions of Lyme disease vaccines.
Lyme disease (LD) represents a significant public health challenge in North America and Eurasia. The persistent increase in its incidence may create an opportunity for vaccines to gain broader acceptance. Recent years have seen notable advances in vaccine development. However, achieving a balance between broad-spectrum protection and durable immunity remains a critical bottleneck. This article is presented as a narrative review that systematically summarizes recent progress in Lyme disease vaccine research worldwide, with particular emphasis on the strengths and limitations of approved and investigational candidates. Unlike existing reviews, this study integrates recent clinical investigations of multivalent vaccine candidates with breakthrough advances across diverse vaccine platforms, yielding a comprehensive and current synthesis. We identify critical challenges in contemporary vaccine development and propose actionable solutions. Our forward-looking perspective centers on a triangular strategy that integrates antigen multivalency, platform personalization, and geographical customization, providing a conceptual framework to guide future LD immunoprophylaxis research.
2026-06-21 | Natural antibodies induced by host gut microbiota modulate tick microbiota, inhibiting Borrelia colonization.
The gut microbiome undergoes natural selection pressure, likely because it can affect infection resistance by stimulating natural antibody (NAb) production, notably against the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal). In our study, we explored whether particular glycans, such as α-Gal, from specific host microbiota components could trigger NAbs that, once ingested by Ixodes ricinus ticks during the blood meal, are capable of cross-reacting with bacterial strains in the tick microbiota that share these glycans. Such interactions might alter the tick microbiota and reduce Borrelia afzelii colonization in ticks. When mice were orally administered various Escherichia coli strains, it triggered the stimulation of NAbs and resulted in strain-specific alterations in the tick microbiota. These changes effectively decreased Borrelia colonization in the tick vector. Additionally, vaccination with the glycan α-Gal induced notable shifts in the tick microbiota and similarly reduced Borrelia colonization. Reduced Borrelia colonization was associated with shifts in bacterial diversity, abundance, and microbial network properties. The study provides evidence that natural mechanisms, such as the production of NAb in response to the host gut microbiome, can modulate the microbiota of disease vectors and reduce pathogen colonization within the vector. These findings offer new insights into potential strategies for reducing the transmission of vector-borne diseases through modulation of the host gut microbiome.
2026-05-17 | Developing a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rationale adjuvant selection.
Rational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacterium Borrelia burgdorferi (Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no approved human vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S, with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy after Bb infection. We identified Alum-CpG and Alum-αGal to elicit the highest titers of CspZ-YAC187S-dependent protective antibodies and robust levels of protection, but through distinct mechanisms of immunomodulation. We demonstrated that immunization with Alum-CpG formulated CspZ-YAC187S provided up to nine months of protective bactericidal antibody titers, as well as recall-memory response to prevent LD after natural infection. Immunity was linked to elevated levels of IgG1 memory cells in the vaccine-triggered immune responses. This work thus identified a durable, memory immunity-driven LD vaccine, ultimately paving the road to understand the mechanisms of rationale adjuvant selection for vaccine development.
proteins
2026-07-15 | Single-step immunoblot tests with recombinant protein antigens for detecting IgG and IgM antibodies in Lyme disease.
Serodiagnosis is important in Lyme disease (LD). Until recently, this commonly required two separate tests termed the standard two-tier tests (STTTs). One-step immunoblot (IB) tests utilizing recombinant protein targets from multiple Borrelia species and strains that may simplify the serodiagnosis of LD are now described. Specificity of the IB tests was established with 425 sera from healthy persons and 387 sera from persons with potentially confounding infections and medical conditions. Test sensitivities were determined with (i) 90 sera from patients with different stages of LD from the US Centers for Disease Control and Prevention (CDC), and (ii) 290 prospectively banked sera from patients with acute-stage LD from the Bay Area Lyme Foundation's Lyme Disease Biobank (BALDB). The IgG IB test was more sensitive than a US Food and Drug Administration (FDA)-cleared STTT for detecting IgG antibodies in stage 1 LD sera from the CDC's test panel (P = 0.002). The diagnostic performance of the IgG and IgM IB tests demonstrated significantly greater overall sensitivity than the comparable FDA-cleared STTTs for detecting IgG and/or IgM antibodies in the 290 BALDB sera (P = 0.00004). The IgG IB test was also more sensitive than the IgG STTT for detecting IgG antibodies in the 290 BALDB sera (P < 0.000001). The IgG and IgM IB tests were additionally more sensitive than IgG and IgM STTTs for detecting IgG and/or IgM antibodies in BALDB sera from 189 patients with erythema migrans (P = 0.03). The IB tests described here form the basis for one-step IgG and IgM IB tests, termed iDart IgG and IgM IB tests, cleared by the FDA for LD diagnosis.IMPORTANCEThe immunoblot (IB) tests described here are one-step tests that separately detect IgG and IgM antibodies for the serological diagnosis of Lyme disease in the United States. The IB tests are more sensitive than a common standard two-tier test for detecting antibodies in early-stage Lyme disease. This can assist in the diagnosis of Lyme disease when antibodies have not yet reached their maximum concentration in patient sera.
2026-05-18 | A lipid-binding protein in black-legged tick saliva selectively recognizes Borrelia burgdorferi lipids.
A proteomic analysis of Ixodes scapularis nymph saliva identified 252 proteins, including six tubular lipid-binding proteins (TULIPs). Comparing nymphs fed on mice that were uninfected or infected with Borrelia burgdorferi, twelve salivary proteins showed significant differences in the amounts detected, including XP_040079658.2, which we refer to as TULIP2. Considering the known immunity-related functions of some TULIPs, we expressed and purified TULIP2 from Escherichia coli and analyzed its interaction with B. burgdorferi lipids. The purification of TULIP2 from E. coli presented many obstacles, due to insolubility, which is consistent with previous reports from studies of other TULIP family members. The binding results showed specificity for B. burgdorferi lipids, with evidence for cholesteryl β-galactoside as a major binding target. Molecular modeling of TULIP2 did not show any strong lipid binding sites. We used molecular dynamics simulation of TULIP2 to explore its conformational landscape by thermal unfolding. The earliest unfolding intermediate opened a hydrophobic pocket to which cholesteryl β-galactoside was predicted to bind strongly. We propose that a specific lipid bilayer interaction with TULIP2 triggers the opening of the ligand-binding site.
2026-05-05 | Borrelia burgdorferi sensu lato Employs Several Escape Mechanisms to Bypass the Human Defense System.
Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) through Ixodes tick bites, presents diverse clinical manifestations and may lead to persistent symptoms. This review summarizes current knowledge on the pathogen-host interactions and immune responses. Early infection can be influenced by tick saliva, which suppresses local host defense and promotes spirochete survival, and by pattern recognition receptors activating proinflammatory cascades. Bbsl employs a variety of immune evasion strategies, notably impairing antigen presentation-through disruption of MHC II and IFN-γ pathways-and continuously varying surface antigens to hinder long-lasting antibody formation. Autophagy plays a central role in modulating inflammation and T helper 17 adaptive immune responses, representing an underappreciated mechanism potentially influencing disease outcome. Adaptive immunity in LB is characterized by robust but often dysregulated humoral and cellular responses, with transient germinal centers and enduring IgM production contributing to incomplete pathogen clearance. Persistent immune defects include impaired long-term B cell memory, suppressed T cell activation, and ongoing immunosuppression after pathogen clearance. Similar patterns are observed in other postinfectious fatigue syndromes. Despite advances, gaps remain in understanding mechanisms of Bbsl persistence and the immunopathology underlying chronic disease, challenging diagnosis and therapy. Emerging molecular and cellular approaches offer new avenues to address immunity, diagnostics, and prevention. A multidisciplinary effort will be needed to improve long-term patient outcomes in the evolving epidemiology of LB.
2026-03-27 | Innate Immune Evasion of Lyme Disease Pathogen Drives Alzheimer-Like Pathology.
The amyloid β (Aβ) peptide is the main component of amyloid plaques in Alzheimer's disease (AD). Growing evidence has pointed to a role for Aβ as an antimicrobial peptide (AMP). However, the interactions of Aβ with neurotropic pathogens and host evasion strategies have remained largely unexplored. Using quantitative proteomic analysis of patient cerebrospinal fluid (CSF), advanced biochemical methods, and four different 3D brain models, ranging from blood-brain barrier (BBB) microfluidic systems to 3D neurovascular networks, we show that Lyme neuroborreliosis (LNB) Borrelia spp. induce molecular and immunological alterations in the central nervous system (CNS) that resemble key pathological features of AD. These include upregulation of the complement cascade and a decrease in CSF Aβ levels. By assessing the antimicrobial action of Aβ against Borrelia spp., we demonstrate that Aβ acts as a pre-opsonin by promoting complement activation on microbial surfaces. We also show that LNB Borrelia spp. exhibit unique survival strategies that reduce Aβ binding and block oligomerization, while halting complement attack by recruiting complement regulator factor H. This facilitates bacterial adhesion to the BBB, and modulation of glial and cytokine responses, fostering CNS invasion. Our findings reveal a previously unrecognized mechanism of bacterial immune escape spanning the entire invasion pathway from the BBB to neuronal compartments, demonstrating that LNB Borrelia spp. evade Aβ-mediated antimicrobial action by interfering with opsonization and oligomerization of the peptide. Collectively, these findings provide a direct mechanistic link between pathogen immune evasion, Aβ dynamics, and neuroinflammatory cascades, advancing our understanding of infection-induced neuropathology, offering insights into novel potential therapeutic targets for AD and neuroborreliosis.
2026-02-25 | EXPRESS: A Comprehensive Review of Lyme disease in Latin America.
Lyme disease (LD) is caused by a bacterial genospecies complex named Borrelia burgdorferi sensu lato (s.l.), which includes B. burgdorferi sensu stricto (B.b.s.s). Originally described in North America, LD has also been described in other parts of the Northern Hemisphere, and in Eurasia. Different B.b.s.l. species, transmitted through geographically diverse tick vectors, are associated with different clinical presentations of the disease. In recent years, the incidence and the endemic range of LD have steadily expanded to include areas of the world with tropical climate, including Latin American countries.Challenges in serological diagnosis. Inconsistent confirmatory results, despite clinical diagnosis, could be explained by antigenic differences between these new species in these countries, with American strains used in the elaboration of commercial tests. This could explain indeterminate Western blots and polymerase chain reactions in detecting suspected LD cases.Novel Borrelia taxons may impact the reservoir host spectrum, including mammals, birds, and other animals. Different species of Ixodes ticks are found in Latin America, where I. scapularis is absent, and they could serve as vectors. New genospecies of B.b.s.l. and the scarce information about its pathogenicity, reservoirs and vectors, highlights the importance of further studies tp elucidate their genetic differences in the context of the development of innovative diagnostic and clinical approaches.Knowledge gaps and the need for prospective and rigorous studies, to determine the presence, or not, of LD in this region, warrant call for research providing new insights into the basic biology and epidemiology, and clinical manifestations in this region.
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2026-07-28 | Prevalence and Associated Factors of Borrelia burgdorferi Sensu Lato Exposure in Humans and Infection in Questing Ixodes Ticks in China: A Systematic Review and Meta-Analysis.
Lyme borreliosis has been reported across China, but data on Borrelia burgdorferi sensu lato exposure in humans and infection in questing Ixodes ticks remains fragmented and heterogeneous. This systematic review and meta-analysis aimed to estimate the pooled seroprevalence of B. burgdorferi sensu lato exposure in humans and infection prevalence in questing or unfed Ixodes ticks in China and to explore potential sources of heterogeneity. Six English- and Chinese-language databases were searched from inception to 10 September 2025. Eligible cross-sectional studies reported both the number examined and the number positive, with a minimum sample size of 30. Human analyses were restricted to serological evidence, whereas tick analyses included questing or unfed Ixodes ticks collected from vegetation or the environment. Random-effects models, subgroup analyses, and univariate random-effects meta-regression were applied. A total of 186 studies were included, of which 167 reported human data, 22 reported PCR-based data from questing Ixodes ticks, and 3 reported both human and tick data. The pooled human seroprevalence was 7% (95% CI: 6-8%), and the pooled PCR-confirmed infection prevalence in questing Ixodes ticks was 20% (95% CI: 10-32%). Substantial heterogeneity was observed in both analyses. For questing Ixodes ticks, infection prevalence showed marked geographical heterogeneity, with the highest pooled estimate observed in Northeastern China. In univariate meta-regression, Northern China showed a significantly lower estimate than Northeastern China, whereas sampling year, reported Borrelia genospecies, and Ixodes species were not significantly associated with pooled prevalence. Leave-one-out analyses indicated that the pooled estimates were not driven by any single study. These findings demonstrate that human exposure and environmental circulation of B. burgdorferi sensu lato have been documented across multiple regions of China but remain highly heterogeneous.
2026-05-24 | Evaluation of EcoCRM, virus-like particles, and mRNA as vaccine platforms against Borrelia burgdorferi.
Lyme disease (LD) is the most prevalent vector-borne disease in the United States, impacting ∼476,000 individuals annually with increasing incidence. Prevention relies on personal protective measures such as insecticides and tick checks, underscoring the need for new preventatives such as vaccines. In this work, the importance of vaccine platform in LD vaccine development efforts was evaluated using non-lipidated OspA as model antigen. Recombinant OspA conjugated to CRM197 (EcoCRM OspA), a virus-like particle vaccine utilizing SpyTag and SpyCatcher (OspA-SpyVLP), and an mRNA-based vaccine construct (OspA mRNA) were evaluated and compared in C3H mice using the needle injection challenge model. To determine immunogenicity, anti-OspA and anti-B. burgdorferi antibodies were quantified via ELISA and further assessed by measuring IgG subclass, antibody avidity, and presence of antibody secreting cells. All vaccine formulations were immunogenic and led to the release of similar levels of antigen-specific IgG in serum during the duration of the experiment. However, there were significant differences around two week post-boost in the presence of antibody secreting cells, ratio of IgG1/IgG2 subclasses, and antibody avidity between platforms. Protection was measured using PCR and darkfield microscopy to determine organ positivity post-challenge. Vaccination with recombinant non-lipidated OspA and OspA-SpyVLP significantly reduced the number of positive organs compared to the PBS challenged control group. Lastly, in vitro borreliacidal activity was quantified via darkfield microscopy and the highest borreliacidal activity was observed using OspA-SpyVLP sera, with titers 16-fold higher than recombinant OspA. Altogether, these data indicated that selection of vaccine platform/formulation influenced the immunogenicity and efficacy of OspA-based LD vaccines and should be considered during development.
2026-02-19 | Non-invasive ovulation tracking enables genetic engineering in wild rodents.
Many non-model rodent species are inaccessible to genetic engineering due to our limited understanding of their reproductive biology. Here, we present a low-cost, camera-based estrous-tracking technology that enables transgenesis in the white-footed mouse Peromyscus leucopus, a key reservoir for Lyme disease. We demonstrate the efficient generation of pregnant and pseudopregnant mice via timed ovulation, provide protocols for embryo generation, cultivation, microinjection, and transplantation as well as an accurate developmental timeline, and report the first engineered Peromyscus. The same technology successfully tracked conserved estrous-linked cycling behavior in other rodents, including hamsters. Finally, estrous tracking differentiated reproductively healthy, geriatric female Peromyscus from those with declining fertility based solely on their activity, providing a non-invasive method for studying reproductive senescence. Collectively, these tools represent a critical resource for engineering non-model rodents, advance the long-lived Peromyscus as a model organism, and will prove essential to heritably immunizing wild rodent populations against Lyme disease.
2026-01-01 | P-1485. Safety and Immunogenicity of mRNA-1982 and mRNA-1975, mRNA Vaccine Candidates for Prevention of Lyme Disease in Healthy Adults: Interim Results of a Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Trial
Abstract Background The incidence of Lyme disease, caused by infection with Borrelia bacteria, continues to rise globally. Previously developed Lyme disease vaccines based on Borrelia OspA antigens elicited antibody responses that correlated with protection; however, no Lyme disease vaccine is currently available for use in humans. Two investigational mRNA vaccines encoding OspA antigens and formulated in a lipid nanoparticle are in development: a monovalent vaccine (mRNA-1982) that covers serotype 1, and a heptavalent vaccine (mRNA-1975) that covers serotypes 1-7. Methods This ongoing Phase 1/2, randomized, observer-blind, placebo-controlled dose-ranging trial in healthy adults 18-70 years of age evaluated the safety and immunogenicity of mRNA-1982 and mRNA-1975 at up to 4 dose levels administered as a 3-injection series at 0, 2, and 6 months (NCT05975099). An interim analysis was conducted with follow-up through 28 days after the 3rd injection for safety and reactogenicity evaluation. Immunogenicity was evaluated by serotype-specific anti-OspA IgG binding antibody responses and by levels of LA-2 equivalent antibody (serotype 1 only). Results At the interim analysis, 745 of 806 enrolled participants completed the 3-injection study vaccine series. Approximately 1% of enrolled participants were seropositive at baseline for prior Borrelia infection. Both mRNA-1982 and mRNA-1975 elicited predominantly mild to moderate reactogenicity that was dose-dependent and increased with each successive injection, with no safety concerns identified. Serotype-specific anti-OspA IgG binding antibody geometric mean-fold rise from baseline and proportions of participants with high levels of LA-2 equivalent antibody responses (≥75% and ≥90% LA-2 inhibition) increased in a dose-dependent manner and with each successive injection across the vaccine groups, compared with no increase in the placebo group. Conclusion Interim data from this ongoing Phase 1/2 trial show that both mRNA-1982 and mRNA-1975 are generally safe and elicit dose-dependent reactogenicity and immunogenicity that increased with each of 3 successive injections. These data will inform the product(s), regimen(s) and dose range(s) to be evaluated in future clinical trials. Disclosures Nina H. Lin, MD, Moderna, Inc: Stocks/Bonds (Public Company) Christina Dold, PhD, Moderna: Stocks/Bonds (Public Company) Meredith Finn, PhD, Moderna: Stocks/Bonds (Public Company) Jacqueline Dooley, BA, Moderna: Stocks/Bonds (Public Company) Rujun Teng, MS, Moderna Inc.: Advisor/Consultant Emma Viscidi, PhD, MHS, ModernaTX: Employee|ModernaTX: Stocks/Bonds (Public Company) Anthony Rizk, PharmD, MBA, Moderna, Inc.: Employee of Moderna, Inc.|Moderna, Inc.: Stocks/Bonds (Public Company) Haixing Wang, PhD, Moderna, Inc.: Stocks/Bonds (Public Company) Doran Fink, MD, PhD, ModernaTX, Inc.: Employee|ModernaTX, Inc.: Stocks/Bonds (Public Company)
2025-12-05 | Polyvalent mRNA vaccine targeting outer surface protein C affords multi-strain protection against Lyme disease.
There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, Borrelia burgdorferi, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.
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