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Lyme disease, caused by Borreliella burgdorferi and related species , is a growing health threat to companion animals across North America and Europe. Vaccination is an important preventive tool used widely in dogs living in, or near, endemic regions. In this report, we assessed anti-outer surface protein (Osp) A and anti-OspC antibody responses in B. burgdorferi -infected and -naïve mice (C3H/HeN) after immunization with a murine-optimized single dose of the Lyme disease subunit vaccine, Vanguard crLyme. crLyme is comprised of OspA and an OspC chimeritope-based immunogen designated as CH14. Mice that were infected and immunized developed higher levels of anti-OspC antibodies (Abs) than those infected only or that received one vaccine dose. The anti-OspC Abs that developed in the infected/immunized mice bound to all OspC variants tested ( n = 22), whereas OspC Abs in serum from infected mice bound predominantly to the OspC variant (type A) produced by the infecting B. burgdorferi strain. Consistent with the absence of OspA expression in infected mammals, none of the infected mice developed Abs to OspA and did not develop anti-OspA Abs after single dose immunization. Lastly, serum from infected/immunized mice displayed significantly higher and broader killing activity than serum from non-immunized infected mice. The results of this study demonstrate that a single vaccination of actively infected mice results in strong anti-OspC Ab responses. This study contributes to our understanding of Ab responses to vaccination in actively infected mammals., Competing Interests: R.T.M. is a co-inventor of the crLyme vaccine and receives royalties from the VCU Intellectual Property Foundation. This study was supported, in part, by a grant from Zoetis Petcare. The sponsor played no role in the study design, data interpretation, or manuscript preparation.

Background: Incidence rates of Lyme borreliosis, a tickborne disease attributed to infection by Borrelia species, are increasing, and limitations to existing treatments potentiate the possibility of severe outcomes. Nevertheless, there are no licensed vaccines for Lyme borreliosis prevention in humans. This study investigated the immunogenicity and safety of a booster dose of VLA15, an investigational outer surface protein A (OspA)-based Lyme borreliosis vaccine that has previously shown safety and immunogenicity when administered as a primary vaccination series, following a primary VLA15 vaccination series., Methods: We report the results of the booster phase of a randomised, observer-blinded, placebo-controlled, multicentre, phase 2 study that enrolled healthy adults aged 18-65 years from five US clinical study centres to receive 135 μg or 180 μg VLA15 or placebo at months 0, 2, and 6 in the main study phase. Participants who received 180 μg VLA15 in the main study phase and did not have relevant protocol deviations were eligible for the booster phase (months 18-30). Participants were randomly reassigned (2:1) to receive an intramuscular injection of a VLA15 booster or placebo 1 year after the completion of primary vaccination (month 18) via a randomisation list generated by an unmasked statistician with a block size of six. Individuals involved in data safety monitoring, rerandomisation, vaccine handling, and vaccine accountability were unmasked; the study sponsor and statisticians were only unmasked after analysis of data up to 1 month after booster administration. All other individuals remained masked throughout the booster phase. The outcomes for the booster phase were the immunogenicity (evaluated in the booster per-protocol population) and safety (evaluated for all participants who received the booster) of the booster dose up to month 30. The study is registered at ClinicalTrials.gov (NCT03970733) and is completed., Findings: Between Feb 4 and March 23, 2021, 58 participants (28 men and 30 women) were screened, randomly assigned, and received VLA15 (n=39) or placebo (n=19). One participant in the placebo group was lost to follow-up. The IgG geometric mean titres for each OspA serotype (serotypes 1-6) in the VLA15 group peaked at 1 month after the booster dose (1277·0 U/mL [95% CI 861·8-1892·3] to 2194·5 U/mL [1566·8-3073·7] vs 23·6 U/mL [18·1-30·8] to 36·8 U/mL [26·4-51·3] in the placebo group [p<0·0001 for all serotypes]), remained elevated at month 24 (137·4 U/mL [95·8-196·9] to 265·8 U/mL [202·9-348·2] vs 22·3 U/mL [17·7-28·0] to 29·1 U/mL [20·8-40·6] in the placebo group; p<0·0001 for all serotypes), and declined by month 30 (54·1 U/mL [38·6-75·7] to 101·6 U/mL [77·6-133·1] vs 21·9 U/mL [18·0-26·6] to 24·9 U/mL [19·0-32·6] in the placebo group; p<0·0001 for all serotypes except serotype 1 [p=0·0006]). Solicited local adverse events were reported more frequently in the VLA15 group (35 [92%, 95% CI 79-97] of 38 participants) than the placebo group (six [32%, 15-54] of 19 participants; p<0·0001) after booster vaccination. There was no significant difference in the frequency of solicited systemic adverse events between groups (20 [59%, 42-74] of 34 participants in the VLA15 group vs six [38%, 18-61] of 16 participants in the placebo group). Related unsolicited adverse events (none severe) were reported by two (5%, 1-17) of 39 participants in the VLA15 group and none (0%, 0-17) of 19 participants in the placebo group. There were no severe solicited local or systemic adverse events or deaths during the study., Interpretation: A booster dose of VLA15 is safe and induces substantial anamnestic immune responses against all six OspA serotypes. As with previously investigated OspA-based Lyme borreliosis vaccines, waning immune responses were observed with VLA15, and annual boosters might therefore be required., Funding: Valneva., Competing Interests: Declaration of interests SKG, MS, KD, LW, VK, MO, RH, WB, SE-L, and NB are current or former employees of Valneva and may hold stock or stock options. AK, JL-S, and UD are paid consultants for Valneva., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Rising Lyme borreliosis incidence rates, potential for severe outcomes, and limitations in accurate and timely diagnosis for treatment initiation suggest the need for a preventive vaccine; however, no vaccine is currently available for human use. We performed two studies in adults to optimise the dose level and vaccination schedule for VLA15, an investigational Lyme borreliosis vaccine targeting outer surface protein A (OspA) serotypes 1-6, which are associated with the most common pathogenic Borrelia species in Europe and North America., Methods: Both randomised, observer-blind, placebo-controlled, multicentre phase 2 studies included participants aged 18-65 years without recent history of Lyme borreliosis or tick bites. Study one was conducted at nine clinical research and study centre sites in the USA (n=6), Germany (n=2), and Belgium (n=1); study two was conducted at five of the study one US sites. Based on a randomisation list created by an unmasked statistician for each study, participants were randomly assigned via an electronic case report form randomisation module to receive 90 μg (study one only), 135 μg, or 180 μg VLA15 or placebo by intramuscular injection at months 0, 1, and 2 (study one) or 0, 2, and 6 (study two). Study one began with a run-in phase to confirm safety, after which the Data Safety Monitoring Board recommended the removal of the 90 μg group and continuation of the study. In the study one run-in phase, randomisation was stratified by study site, whereas in the study one main phase and in study two, randomisation was stratified by study site, age group, and baseline B burgdorferi (sensu lato) serostatus. All individuals were masked, other than staff involved in randomisation, vaccine preparation or administration, or safety data monitoring. The primary endpoint for both studies was OspA-specific IgG geometric mean titres (GMTs) at 1 month after the third vaccination and was evaluated in the per-protocol population. Safety endpoints were evaluated in the safety population: all participants who received at least one vaccination. Both studies are registered at ClinicalTrials.gov (study one NCT03769194 and study two NCT03970733) and are completed., Findings: For study one, 573 participants were screened and randomly assigned to treatment groups between Dec 21, 2018, and Sept, 26, 2019. For study two, 248 participants were screened and randomly assigned between June 26 and Sept 3, 2019. In study one, 29 participants were assigned to receive 90 μg VLA15, 215 to 135 μg, 205 to 180 μg, and 124 to placebo. In study two, 97 participants were assigned to receive 135 μg VLA15, 100 to 180 μg, and 51 to placebo. At 1 month after the third vaccination (ie, month 3), OspA-specific IgG GMTs in study one ranged from 74·3 (serotype 1; 95% CI 46·4-119·0) to 267·4 units per mL (serotype 3; 194·8-367·1) for 90 μg VLA15, 101·9 (serotype 1; 87·1-119·4) to 283·2 units per mL (serotype 3; 248·2-323·1) for 135 μg, and 115·8 (serotype 1; 98·8-135·7) to 308·6 units per mL (serotype 3; 266·8-356·8) for 180 μg. In study two, ranges at 1 month after the third vaccination (ie, month 7) were 278·5 (serotype 1; 214·9-361·0) to 545·2 units per mL (serotype 2; 431·8-688·4) for 135 μg VLA15 and 274·7 (serotype 1; 209·4-360·4) to 596·8 units per mL (serotype 3; 471·9-754·8) for 180 μg. Relative to placebo, the VLA15 groups had more frequent reports of solicited local adverse events (study one: 94%, 95% CI 91-96 vs 26%, 19-34; study two: 96%, 93-98 vs 35%, 24-49 after any vaccination) and solicited systemic adverse events (study one: 69%, 65-73 vs 43%, 34-52; study two: 74%, 67-80 vs 51%, 38-64); most were mild or moderate. In study one, unsolicited adverse events were reported by 52% (48-57) of participants in the VLA15 groups and 52% (43-60) of those in the placebo groups; for study two these were 65% (58-71) and 69% (55-80), respectively. Percentages of participants reporting serious unsolicited adverse events (study one: 2%, 1-4; study two: 4%, 2-7) and adverse events of special interest (study one: 1%, 0-2; study two: 1%, 0-3) were low across all groups. A single severe, possibly related unsolicited adverse event was reported (worsening of pre-existing ventricular extrasystoles, which resolved after change of relevant concomitant medication); no related serious adverse events or deaths were reported., Interpretation: VLA15 was safe, well tolerated, and elicited robust antibody responses to all six OspA serotypes. These findings support further clinical development of VLA15 using the 180 μg dose and 0-2-6-month schedule, which was associated with the greatest immune responses., Funding: Valneva., Competing Interests: Declaration of interests NB, LW, VK, MO, NW, RH, MS, KD, SE-L, and WB are current or former employees of Valneva and may hold stock or stock options. UD, AK, and JL-S are paid consultants for Valneva., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The rising prevalence of Lyme disease (LD) in North America and Europe has emerged as a pressing public health concern. Despite the availability of veterinary LD vaccines, no vaccine is currently available for human use. Outer surface protein C (OspC) found on the outer membrane of the causative agent, Borrelia burgdorferi , has been identified as a promising target for LD vaccine development due to its sustained expression during mammalian infection. However, the efficacy and immunological mechanisms of LD vaccines solely targeting OspC are not well characterized. In this study, we developed an attenuated Vaccinia virus (VV) vectored vaccine encoding type A OspC (VV-OspC-A). Two doses of the VV-OspC-A vaccine conferred complete protection against homologous B. burgdorferi challenge in mice. Furthermore, the candidate vaccine also prevented the development of carditis and lymph node hyperplasia associated with LD. When investigating the humoral immune response to vaccination, VV-OspC-A was found to induce a robust antibody response predominated by the IgG2a subtype, indicating a Th1-bias. Using a novel quantitative flow cytometry assay, we also determined that elicited antibodies were capable of inducing antibody-dependent cellular phagocytosis in vitro . Finally, we demonstrated that VV-OspC-A vaccination generated a strong antigen-specific CD4 + T-cell response characterized by the secretion of numerous cytokines upon stimulation of splenocytes with OspC peptides. This study suggests a promising avenue for LD vaccine development utilizing viral vectors targeting OspC and provides insights into the immunological mechanisms that confer protection against B. burgdorferi infection.

Lyme disease (LD) is an emerging zoonotic infection that is increasing in incidence in North America, Europe, and Asia. With the development of safe and efficacious vaccines, LD can potentially be prevented. Vaccination offers a cost-effective and safe approach for decreasing the risk of infection. While LD vaccines have been widely used in veterinary medicine, they are not available as a preventive tool for humans. Central to the development of effective vaccines is an understanding of the enzootic cycle of LD, differential gene expression of Borrelia burgdorferi in response to environmental variables, and the genetic and antigenic diversity of the unique bacteria that cause this debilitating disease. Here we review these areas as they pertain to past and present efforts to develop human, veterinary, and reservoir targeting LD vaccines. In addition, we offer a brief overview of additional preventative measures that should employed in conjunction with vaccination.

Outer surface protein A (OspA) is a Borrelia lipoprotein and an established Lyme disease vaccine target. Admixing non-lipidated, recombinant B. burgdorferi OspA with liposomes containing cobalt porphyrin-phospholipid (CoPoP) resulted in rapid, particulate surface display of the conformationally intact antigen. Particleization was serum-stable and led to enhanced antigen uptake in murine macrophages in vitro. Mouse immunization using CoPoP liposomes that also contained a synthetic monophosphoryl lipid A (PHAD) elicited a Th1-biased OspA antibody response with higher IgG production compared to other vaccine adjuvants. Antibodies were reactive with intact B. burgdorferi spirochetes and Borrelia lysates, and induced complement-mediated borreliacidal activity in vitro. One year after initial immunization, mice maintained high levels of circulating borreliacidal antibodies capable of blocking B. burgdorferi transmission from infected ticks to human blood in a feeding chamber., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A total of 143 horses were included in a study to test a commercial vaccine against Lyme borreliosis. The vaccine contained three different antigens (outer surface protein A, OspA) to prevent the infection with spirochetes - B.burgdorferi sensu stricto, B. afzelii and B. garinii. Horses in Group A (49 animals) received two vaccinations on days 0 and 14 and a booster on day 365, whereas 50 horses in Group B received an additional booster vaccination on day 180. Group C (44 animals) was not immunized. Total antibody levels and specific OspA antibody responses were assessed quantitatively and qualitatively in two-month intervals over 13-month period. Vaccinees in Groups A and B developed high OspA antibodies levels, whereas horses in Group C did not show specific antibody responses. The additional vaccination applied in Group B enhanced the specific OspA antibody response significantly and prevented its rapid decline., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lyme disease (LD) accounts for over 70% of tick-borne disease reported in the United States. The disease in humans is characterized by skin rash, arthritis, cardiac and neurological signs. Vaccination is the most efficient preventive measure that could be taken to reduce the incidence of the LD worldwide; however, at present no vaccine is available. In this study, evaluation of the Borrelia burgdorferi BB0172-derived peptide (PepB) in conjugated formulations was investigated as a vaccine candidate in murine model of LD. In brief, PepB was conjugated to the Cross-Reacting Material 197 (CRM197) and to Tetanus Toxoid heavy chain (TTHc) molecules, and subsequently used to immunize C3H/HeN mice. Following the challenge with 10 5 spirochetes/mouse via subcutaneous inoculation, TTHc:PepB construct showed protection in 66% of the immunized animals. Hence, to further evaluate the efficacy of TTHc:PepB, immunized mice were challenged with B. burgdorferi using the tick model of infection. The outcome of this experiment revealed that serum from TTHc:PepB immunized mice was borrelicidal. After tick infection, bacterial burden was significantly reduced (over 70%) in vaccinated animals when compared with the control groups regardless of whether the mice were infested 8 or 12-weeks post-priming. Therefore, we conclude that PepB conjugated antigens can serve as an alternative to prevent LD; nevertheless, further studies will be needed to dissect the mechanisms by which anti-PepB IgG antibodies are able to kill B. burgdorferi in vitro and in vivo to further advance in the development of formulations and delivery alternative to generate a safe anti-LD vaccine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Escherichia coli is the mainstay tool for fundamental microbiology research due to its ease of cultivation and safety. Auxotrophic strains of the K-12 and B lineages of E. coli are the organisms of choice to produce recombinant proteins. Components present in the cell envelope of bacteria are also potent immune modulators and have been used to develop adjuvants. We used live E. coli, after induction of recombinant protein expression, to develop a vehicle which has a dualistic function of producing vaccine while presenting itself as the adjuvant to deliver oral vaccines against a number of infectious diseases, including Lyme disease. Here, we give an example using E. coli expressing B. burgdorferi Outer Surface Protein A, which was proven effective in reducing B. burgdorferi burden in infected ticks after a 5-year field trial of a baited formulation containing this reservoir targeted vaccine.

Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Borrelia burgdorferi, B. garinii, and B. afzelii are all agents of Lyme disease in different geographic locations. If left untreated, Lyme disease can cause significant and long-term morbidity, which may continue after appropriate antibiotic therapy has been administered and live bacteria are no longer detectable. The increasing incidence and geographic spread of Lyme disease are renewing interest in the vaccination of at-risk populations. We took the approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that, unlike the parental strain, are avirulent in mice. Mice vaccinated with both strains were protected against a challenge with the parental strain and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. In ticks, the homologous strain was eliminated but the heterologous strain was not, suggesting that the vaccines generated a response to antigens that are produced by the bacteria both early in mammalian infection and in the tick. Partial protection against B. garinii infection was also conferred. Protection was antibody mediated, and reactivity to a variety of proteins was observed. These experiments suggest that live attenuated B. burgdorferi strains may be informative regarding the identification of protective antigens produced by the bacteria and recognized by the mouse immune system in vivo Further work may illuminate new candidates that are effective and safe for the development of Lyme disease vaccines., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Aim: Study innate and adaptive immunity in patients with migrating erythema, clinical effectiveness ofcombined therapy using Immunovac vaccine and dynamics of immunologic parame- ters as a result of the therapy., Materials and Methods: 37 adult patients with migrating erythema were examined. The patients were divided into 2 groups: 1st gr. (14 individuals) - Immunovac by intranasal-subcutaneous method against the background of basic therapy; 2nd gr. (23 individuals) - 200 mg/day doxycycline therapy for 21 days. Phagocytic activity of blood neutrophils; TLRs expression on mononuclear leukocytes of peripheral blood (PBML) and skin cells in foci by flow cytometry with mAT against TLR2, 3, 4, 5, 6, 7, 8, 9 using flow cytometer FC-500; subpopulation composition of peripheral blood lymphocytes; levels of pro-, anti-inflammation and regulatory cytokines in blood sera by EIA method; IgG, 1gM, IgA in blood sera were studied in patients before treatment and 1 month after therapy., Results: A high level of TLR2, 4, 7, 8 on skin cells in foci, TLR2, 4 - on blood cells; low content of CD95+ and CD25+, high-level of serum IL-lb, IL-2 and IL-4, an increase of general IgE level was detected in patients'with migrating erythema. Immunovac facilitated an increase of CD95+ and CD25+, IFN-y synthesis, reduced the level of general IgE in a more pronounced way than basic therapy., Conclusion: Inclusion of Immunovac into therapy of patients With migrating erythema facilitates increase of clinical effectiveness and correlates with correction of immunologic disorders.

There is currently no Lyme borreliosis vaccine available for humans, although it has been shown that the disease can be prevented by immunization with an OspA-based vaccine (LYMErix). Outer surface protein A (OspA) is one of the dominant antigens expressed by the spirochetes when present in a tick. The Borrelia species causing Lyme borreliosis in Europe express different OspA serotypes on their surface, B. burgdorferi (serotype 1), B. afzelii (serotype 2), B. garinii (serotypes, 3, 5 and 6) and B. bavariensis (serotype 4), while only B. burgdorferi is present in the US. In order to target all these pathogenic Borrelia species, we have designed a multivalent OspA-based vaccine. The vaccine includes three proteins, each containing the C-terminal half of two OspA serotypes linked to form a heterodimer. In order to stabilize the C-terminal fragment and thus preserve important structural epitopes at physiological temperature, disulfide bonds were introduced. The immunogenicity was increased by introduction of a lipidation signal which ensures the addition of an N-terminal lipid moiety. Three immunizations with 3.0 µg adjuvanted vaccine protected mice from a challenge with spirochetes expressing either OspA serotype 1, 2 or 5. Mice were protected against both challenge with infected ticks and in vitro grown spirochetes. Immunological analyses (ELISA, surface binding and growth inhibition) indicated that the vaccine can provide protection against the majority of Borrelia species pathogenic for humans. This article presents the approach which allows for the generation of a hexavalent vaccine that can potentially protect against a broad range of globally distributed Borrelia species causing Lyme borreliosis.

The Borrelia burgdorferi bba64 gene product is a surface-localized lipoprotein synthesized within mammalian and tick hosts and is involved in vector transmission of disease. These properties suggest that BBA64 may be a vaccine candidate against Lyme borreliosis. In this study, protective immunity against B. burgdorferi challenge was assessed in mice immunized with the BBA64 protein. Mice developed a high-titer antibody response following immunization with soluble recombinant BBA64 but were not protected when challenged by needle inoculation of culture-grown spirochetes. Likewise, mice passively immunized with an anti-BBA64 monoclonal antibody were not protected against needle-inoculated organisms. BBA64-immunized mice were subjected to B. burgdorferi challenge by the natural route of a tick bite, but these trials did not demonstrate significant protective immunity in either outbred or inbred strains of mice. Lipidated recombinant BBA64 produced in Escherichia coli was assessed for possible improved elicitation of a protective immune response. Although inoculation with this antigen produced a high-titer antibody response, the lipidated BBA64 also was unsuccessful in protecting mice from B. burgdorferi challenge by tick bites. Anti-BBA64 antibodies raised in rats eradicated the organisms, as evidenced by in vitro borreliacidal assays, thus demonstrating the potential for BBA64 to be effective as a protective immunogen. However, passive immunization with the same monospecific rat anti-BBA64 polyclonal serum failed to provide protection against tick bite-administered challenge. These results reveal the challenges faced in not only identifying B. burgdorferi proteins with potential protective capability but also in producing recombinant antigens conducive to preventive therapies against Lyme borreliosis.

Lyme disease (also called borreliosis) is a prevalent chronic disease transmitted by ticks and caused by Borrelia burgdorferi s. l. spirochete. At least one tick protein, namely TROSPA from I. scapularis, commonly occurring in the USA, was shown to be required for colonization of the vector by bacteria. Located in the tick gut, TROSPA interacts with the spirochete outer surface protein A (OspA) and initiates the tick colonization. Ixodes ricinus is a primary vector involved in B. burgdorferi s. l. transmission in most European countries. In this study, we characterized the capacities of recombinant TROSPA protein from I. ricinus to interact with OspA from different Borrelia species and to induce an immune response in animals. We also showed that the N-terminal part of TROSPA (a putative transmembrane domain) is not involved in the interaction with OspA and that reduction of the total negative charge on the TROSPA protein impaired TROSPA-OspA binding. In general, the data presented in this paper indicate that recombinant TROSPA protein retains the capacity to form a complex with OspA and induces a significant level of IgG in orally immunized rats. Thus, I. ricinus TROSPA may be considered a good candidate component for an animal vaccine against Borrelia.

Lyme disease caused by spirochete Borrelia burgdorferi sensu lato, is a tick-born illness. If the infection is not eliminated by the host immune system and/or antibiotics, it may further disseminate and cause severe chronic complications. The immune response to Borrelia is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies associated with Th1 cell activation. A new experimental vaccine was constructed using non-lipidized form of recombinant B. burgdorferi s.s. OspC protein was anchored by metallochelating bond onto the surface of nanoliposomes containing novel nonpyrogenic lipophilized norAbuMDP analogues denoted MT05 and MT06. After i.d. immunization, the experimental vaccines surpassed Alum with respect to OspC-specific titers of IgG2a, IgG2b isotypes when MT06 was used and IgG3, IgM isotypes when MT05 was used. Both adjuvants exerted a high adjuvant effect comparable or better than MDP and proved themselves as nonpyrogenic., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Lyme disease is caused by the spirochete Borrelia burgdorferi. The enzootic cycle of this pathogen requires that Ixodes spp. acquire B. burgdorferi from infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to control B. burgdorferi; there is no human vaccine available, and existing vector control measures are generally not acceptable to the public. However, if B. burgdorferi could be eliminated from its reservoir hosts or from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. We developed OspA-RTV, a reservoir targeted bait vaccine (RTV) based on the immunogenic outer surface protein A (OspA) of B. burgdorferi aimed at breaking the natural cycle of this spirochete. White-footed mice, the major reservoir species for this spirochete in nature developed a systemic OspA-specific IgG response as a result of ingestion of the bait formulation. This immune response protected white-footed mice against B. burgdorferi infection upon tick challenge and cleared B. burgdorferi from the tick vector. In performing extensive studies to optimize the OspA-RTV for field deployment, we determined that mice that consumed the vaccine over periods of 1 or 4 months developed a yearlong, neutralizing anti-OspA systemic IgG response. Furthermore, we defined the minimum number of OspA-RTV units needed to induce a protective immune response.

Lyme disease is a major human health problem which continues to increase in incidence and geographic distribution. As a vector-borne zoonotic disease, Lyme disease may be amenable to reservoir targeted strategies for control. We have previously reported that a vaccinia virus (VV) based vaccine expressing outer surface protein A (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease, protects inbred strains of laboratory mice against infection by feeding ticks and clears the ticks of infection when administered by gavage. Here we extend these studies to develop an effective bait formulation for delivery of the VV based vaccine and test its characteristics under simulated environmental conditions. We show that this vaccine is efficacious in decreasing acquisition of B. burgdorferi by uninfected larval ticks as well as in decreasing transmission from infected ticks to its natural reservoir, Peromyscus leucopus, when fed to mice in oral baits. Using live, in vivo imaging techniques, we describe the distribution of vaccinia virus infection after ingestion of the baited vaccines and establish the use of in vivo imaging technology for optimization of bait delivery. In summary, a VV based OspA vaccine is stable in an oral bait preparation and provides protection against infection for both the natural reservoir and the tick vector of Lyme disease., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although a wide range of interventions are available for use in reducing the public health burden of Lyme disease, additional tools are needed. Vaccinating mouse reservoirs may reduce the prevalence of spirochetal infection due to the powerful vector and reservoir competence-modulating effects of anti-outer surface protein A (OspA) antibody. A delivery system for an oral immunogen would be required for field trials of any candidate vaccine. Accordingly, we tested candidate bait preparations that were designed to be environmentally stable, attractive to mice, and non-nutritive. In addition, we determined whether delivery of such baits within nest boxes could effectively target white-footed mice. A peanut butter-scented bait was preferred by mice over a blueberry-scented one. At a deployment rate of 12.5 nest boxes per hectare, more than half of resident mice ingested a rhodamine-containing bait, as demonstrated by fluorescent staining of their vibrissae. We conclude that a peanut butter-scented hardened bait placed within simple wood nest boxes would effectively deliver vaccine to white-footed mice, thereby providing baseline information critical for designing field trials of a candidate oral vaccine., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Laboratory-reared beagles were vaccinated with a placebo or a bacterin comprised of Borrelia burgdorferi S-1-10 and ospA-negative/ospB-negative B. burgdorferi 50772 and challenged after 1 year with B. burgdorferi-infected Ixodes scapularis ticks. For the placebo recipients, spirochetes were recovered from 9 (60%) skin biopsy specimens collected after 1 month, and the organisms persisted in the skin thereafter. Ten (67%) dogs also developed joint infection (3 dogs), lameness or synovitis (7 dogs), or B. burgdorferi-specific antibodies (8 dogs). For the vaccine recipients, spirochetes were recovered from 6 (40%) skin biopsy specimens collected after 1 month. However, subsequent biopsy specimens were negative, and the dogs failed to develop joint infection (P = 0.224), lameness/synovitis (P = 0.006), or Lyme disease-specific antibody responses (P = 0.002). The bacterin provided a high level of protection for 1 year after immunization, and the addition of the OspC-producing B. burgdorferi 50772 provided enhanced protection.

Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.

We recently hypothesized that T helper 17 (Th17) cells and their associated cytokines are involved in the development of arthritis following infection with Borrelia burgdorferi. Here, we show that interleukin-23 (IL-23), a survival factor for Th17 cells, is required for the induction of arthritis in mice vaccinated with B. burgdorferi strain 297 and challenged with "Borrelia bissettii." When Borrelia-vaccinated and -challenged mice were given antibodies to the p19 subunit of IL-23, they failed to develop the histopathological changes observed in untreated vaccinated and challenged mice. In addition, viable B. bissettii organisms stimulated the secretion of IL-17 from Borrelia-immune lymph node cells during in vitro culture. When anti-IL-23 p19 antibody was included in cultures of B. bissettii organisms and Borrelia-immune lymph node cells, the production of IL-17 was reduced to levels observed in cultures containing immune cells alone. Taken together, these results support the hypothesis that Th17 cell-associated cytokines are involved in the development of Borrelia-mediated arthritis. These findings provide insight into previously overlooked immune mechanisms responsible for the development of Lyme arthritis.

Using five commercially available vaccines, groups of dogs were vaccinated against Lyme borreliosis and followed for 13 months. A modified vaccination schedule was included in the study in an attempt to induce higher and therefore longer-lasting protective antibody levels during the first year of immunization. Following vaccination antibodies were monitored using ELISA and Western blotting. Serum samples were examined either with antigen preparations derived from either Borrelia burgdorferi s. s., B. garinii or B. afzelii lysates or separately with recombinant OspA derived from the three species. Regardless of the vaccine used the third vaccination induced significantly higher antibody levels. Further analyses of the sera with homologue and heterologue detection systems showed in vitro only a minor cross-reactivity of vaccinal antibodies towards antigens derived from heterologous Borrelia species in vitro and consequently only minimal cross-protection can be expected.

Although pediatric Lyme borreliosis (LB) need not be a separate nosological entity, there are clinically important differences in presentation, antibiotic regimens and outcomes in children, which provide lessons that can be extrapolated to the disease as it affects adults. A large proportion of the worldwide data is obtained from children. The aim of this presentation is not to present an exhaustive review of the pediatric literature, but to review a selection of pediatric studies that have made a significant contribution to our body of knowledge in Lyme borreliosis.

Nearly 100 years ago, Afzelius described a patient with an expanding skin lesion, called erythema migrans, which is now known to be the initial skin manifestation of Lyme borreliosis. Approximately 70 years later, in 1976, epidemiologic evaluation of a cluster of children with arthritis in Lyme, Connecticut led to a complete description of the infection. During the subsequent years, investigators in a number of countries have made remarkable strides in the elucidation of this tick-borne spirochetal infection. The purpose of this review is to discuss the current status of Lyme borreliosis, including areas in which knowledge of the infection is still incomplete.

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

Lyme disease is caused by the spirochete Borrelia burgdorferi, which is transmitted through the bite of infected Ixodes ticks. Vaccination of mice with outer surface protein A (OspA) of B. burgdorferi has been shown to both protect mice against B. burgdorferi infection and reduce carriage of the organism in feeding ticks. Here we report the development of a murine-targeted OspA vaccine utilizing Vaccinia virus to interrupt transmission of disease in the reservoir hosts, thus reducing incidence of human disease. Oral vaccination of mice with a single dose of Vaccinia expressing OspA resulted in high antibody titers to OspA, 100% protection of vaccinated mice from infection with B. burgdorferi, and significant clearance of B. burgdorferi from infected ticks fed on vaccinated animals. The results indicate the vaccine is effective and may provide a manner to reduce incidence of Lyme disease.

Lyme borreliosis, the most common tick-borne disease in both North America and Europe, is acquired through the bite of certain tick species in the genus Ixodes. The number of Ixodes ticks in the environment can be reduced by relatively simple interventions such as removing leaf litter and brush, which increases exposure of the tick to sun and air and takes advantage of the tick's vulnerability to desiccation, or by application of acaricides to property. Deer elimination or exclusion, application of topical acaricides to mice or deer, and application of systemic acaricides to deer are more complex approaches. However, none of these methods for reducing tick numbers, nor any of the recommended personal prevention measures, such as reducing the amount of exposed skin, use of tick repellents on exposed skin or clothing, and frequent tick checks to remove attached ticks expeditiously, has been demonstrated to decrease significantly the incidence of Lyme borreliosis in humans. Only two strategies have been shown to do so. A recombinant outer surface protein A (OspA) vaccine was approximately 80% effective in clinical trials in the United States, and a single 200 mg dose of doxycycline given within 72 hours of an I. scapularis tick bite, was shown to be 87% effective. The OspA vaccine is no longer manufactured due to poor sales. Consequently, single-dose doxycycline prophylaxis is rapidly gaining acceptance in the United States. Limiting single-dose doxycycline to just the highest risk tick bites can be accomplished if the health care provider has learned to differentiate engorged from unengorged I. scapularis ticks. Limitations of single-dose doxycycline prophylaxis are that the majority of patients with Lyme borreliosis do not recall a tick bite, and that there is no evidence that other Ixodes transmitted infections, such as human granulocytic ehrlichiosis, would be prevented. A safe, effective, inexpensive and well-accepted vaccine would be welcome.

CD4(+) CD25(+) T cells are a population of regulatory T cells associated with control of arthritis in anti-interleukin-17 antibody-treated Borrelia-vaccinated and challenged gamma interferon-deficient mice. Here, we present direct evidence that adoptive transfer of enriched CD4(+) CD25(+) T cells from these mice can prevent the development of arthritis in Borrelia-vaccinated and challenged mice. These findings establish a major role for CD4(+) CD25(+) T cells in the prevention of arthritis in Borrelia-vaccinated and challenged animals.

Lyme disease is caused by the spirochete Borrelia burgdorferi and it is the most common vector-borne disease in the United States. Disseminated spirochetes can persist in various tissues and can result in a variety of different disease manifestations. Vaccination trials testing various lipoprotein candidates have yielded mixed results despite the generation of robust antibody titers. Data presented in this report demonstrate that a combination vaccine composed of DbpA, BBK32 and OspC is more effective than single or double component formulations and that the ratio of each component dramatically impacts vaccine efficacy when tested in protection experiments against Borrelia following needle inoculation.

CD4+ CD25+ T cells are a population of regulatory T cells responsible for active suppression of autoimmunity. Specifically, CD4+ CD25+ T cells have been shown to prevent insulin-dependent diabetes mellitus, inflammatory bowel disease, and pancreatitis. Here, we present evidence that CD4+ CD25+ T cells also play a major role in controlling the severity of arthritis detected in Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-gamma degrees ) C57BL/6 mice challenged with the Lyme spirochete. When B. burgdorferi-vaccinated and challenged IFN-gamma degrees mice were treated with anti-interleukin-17 (IL-17) antibody, the number of CD4+ CD25+ T cells increased in the local lymph nodes. Furthermore, histopathologic examination showed the mice to be free of destructive arthritis. When these anti-IL-17-treated B. burgdorferi-vaccinated and challenged mice were also administered anti-CD25 antibody, the number of CD4+ CD25+ T cells in the local lymph nodes decreased. More importantly, severe destructive arthropathy was induced. In addition, delayed administration of anti-CD25 antibody decreased the severity of the arthritis. These results suggest that CD4+ CD25+ T cells are involved in regulation of a severe destructive arthritis induced with an experimental model of vaccination and challenge with B. burgdorferi.

A 25-amino-acid synthetic peptide (C(6) peptide) derived from an immunodominant conserved region (designated IR(6)) of the VlsE protein of Borrelia burgdorferi has been identified and used to construct immunoenzyme-based diagnostic procedures. These procedures have excellent sensitivity and specificity. Previous reports have demonstrated the usefulness of the C(6) peptide as an antigen for the serodiagnosis of human and canine Lyme disease. Results indicated that assays based on the C(6) peptide were nonreactive to sera from vaccinated nonexposed animals. The purpose of the present study was to confirm these results in a controlled trial by testing sera from experimentally vaccinated dogs known to be uninfected. Nine specific-pathogen-free beagles were assigned to one of three vaccine groups, each containing three dogs. Each group received one of three commercial Lyme vaccines: RECOMBITEK Lyme (Merial), LymeVax (Fort Dodge Animal Health), and Galaxy Lyme (Schering-Plough Animal Health). Each animal was administered a total of five doses of vaccine over a period of 39 weeks. Serum samples were collected prior to vaccination and then on a weekly basis from weeks 3 to 18 and from weeks 33 to 43. Selected samples were tested by the immunofluorescence assay (IFA) and the Western blot (WB) assay using whole-cell B. burgdorferi antigen extracts, and the results were compared to those obtained with two immunoenzyme-based procedures formatted by using the C(6) peptide. Serum specimens from all animals were reactive to the IFA and WB assay at week 5 and became highly reactive following the administration of multiple doses of vaccine. All serum specimens were uniformly nonreactive in the C(6) peptide immunoenzyme procedures at all time points throughout the study.

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

The natural history of asymptomatic seroconversion to Borrelia burgdorferi has been unclear. We report here, on the basis of a post hoc assessment, the frequency and outcome of asymptomatic seroconversion to B. burgdorferi in participants of a large Lyme disease vaccine trial. We show that infection with B. burgdorferi may be asymptomatic but that asymptomatic infection is unusual in the United States.

Background: An efficacy trial of an outer-surface protein A (OspA) Lyme disease vaccine demonstrated tolerability and efficacy against laboratory-confirmed Lyme disease after a primary series of 3 doses at 0, 1, and 12 months., Objectives: This extension of the efficacy study assessed the immunogenicity and tolerability of booster vaccinations administered at 24 and/or 36 months after the first vaccination., Methods: This open-label, nonrandomized, single-center, prospective extension, clinical trial was conducted in the general community in New Haven, Connecticut, where Lyme disease is endemic. Blood samples (to determine anti-OspA titer) were collected before administration of the booster doses at months 24 and 36, and at 1 and 12 months after each booster dose was administered. Immune response was assessed via total immunoglobulin G (IgG) anti-OspA antibody titers and the proportion of subjects with titers >or=1400 EL.U/mL. Adverse events (AEs) were recorded by the study volunteers on diary cards., Results: A total of 318 volunteers (173 women and 145 men) received at least 1 booster dose of Lyme disease vaccine, administered at 12 or 24 months after the third vaccination of the primary series (months 24 and 36, in relation to the primary series). Eighty-eight subjects of those who received a month-24 booster received a second booster dose at month 36 (12 months after the first booster). Overall, the mean age of the volunteers was 55 years (range, 19 to 73 years). The demographic characteristics of the groups were similar. Most AEs were limited induration and were rated by investigators and subjects as mild to moderate in severity. Administration of I or 2 booster doses did not elicit any patterns of AEs different from those reported in the efficacy trial. After the first booster dose, all volunteers had an anamnestic response and positive test results for total IgG antibody. Geometric mean titers increased at least 12-fold 1 month after the first booster dose at month 24 or 36. More than 96% of volunteers had titers>1400 EL.U/mL and 100% had titers >400 EL.U/mL (minimum seroprotective level) 1 month after the booster dose at month 24 or 36., Conclusions: All booster doses were well tolerated, and the incidence of AEs did not increase after the second booster dose. The immune response generated after the 3-dose primary series waned; booster doses administered at 12 and/or 24 months after the primary series increased antibody levels above seroprotective levels.

Laboratory testing for B. burgdorferi infection is intended to substantiate a physician's clinical judgment of whether a patient has Lyme disease or not. Cultivation of B. burgdorferi from a patient's skin or blood is the gold standard for demonstration of active infection, but it is expensive and lacks clinical sensitivity. Detection of spirochetal DNA in clinical samples by PCR has better sensitivity, but PCR for B. burgdorferi has not yet been standardized for more routine diagnostic testing. Detection of antibodies to B. burgdorferi is the most practical and common approach for laboratory work-up of a case of suspected Lyme disease. Serologic assays fall short of 100% sensitivity and specificity, however, and examination of a single specimen in time does not discriminate between previous and ongoing infection. Because of a background false positivity even among healthy populations of nonendemic regions, serologic testing is recommended only when there is at least a one in five chance, in the physician's estimation, that the patient has active Lyme disease. The pretest likelihood of the disease is determined by the physician in the context of epidemiologic and clinical facts of the case. This estimate can serve to reassure patients who are at low risk of B. burgdorferi infection but are seeking a Lyme test for complaints of a more nonspecific nature. Although new subunit serologic assays based on recombinant proteins are becoming available commercially, the longstanding two-test approach, in which a positive or indeterminate result with a standardized, sensitive ELISA test is followed by verification with a more specific Western blot assay, still provides the physician with a reasonably accurate and reliable assessment of the presence of antibodies to B. burgdorferi. More recent challenges for serologic testing are seropositivity in the population as the result of immunization with the Lyme disease vaccine and the emergence of new Borrelia species that cause Lyme disease-like illnesses.

Context: The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to licensure., Objective: To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccine's licensure., Design, Setting, and Participants: Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000., Main Outcome Measure: We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine., Results: Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported., Conclusion: Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials.

All current seroassays using cultured Borrelia burgdorferi as their antigen source have been rendered obsolete by the recombinant OspA Lyme disease vaccine. OspA is the major outer surface protein expressed in cultured B. burgdorferi, and any seroassay that uses whole organisms as its antigen source cannot differentiate between subjects who received the vaccine and those who were naturally infected. We developed a new sensitive and specific enzyme-linked immunosorbent assay (ELISA) utilizing recombinant chimeric borrelia proteins devoid of OspA (rNon-OspA) that can be used to detect antibodies to diagnostically important B. burgdorferi antigens in both OspA-vaccinated and nonvaccinated individuals. We tested sera from patients with Lyme disease and with conditions associated with false-positive serologies, OspA-vaccinated individuals, and healthy high-risk workers from an area of endemicity and normal sera from individuals from areas of nonendemicity. The rNon-OspA test was compared with two commercially available whole-cell immunoassays. The rNon-OspA assay is as sensitive and specific as the whole-cell assay (P > 0.05) for detection of anti-B. burgdorferi antibodies. However, the rNon-OspA assay can differentiate between populations comprised of naturally infected and OspA-vaccinated individuals (P < 0.05). Our data demonstrate that this new sensitive rNon-OspA ELISA can be used for the laboratory detection of B. burgdorferi antibodies regardless of vaccination status and could replace existing serologic assays for Lyme disease.

Objective: A recombinant lipoprotein outer surface protein A (OspA) Lyme disease (LD) vaccine (LYMErix) has been shown to be safe and effective in preventing LD in adults and in adolescents 15 years of age and older. Children are at risk for developing LD. This clinical study was conducted to address the safety and immunogenicity of LD vaccine in children 4 to 18 years of age., Methods: A randomized, placebo-controlled clinical trial was conducted at 17 investigational sites in Lyme-endemic areas in the United States. Immunogenicity data from this study also were compared with data obtained from the adult efficacy study. A total of 4090 healthy children and adolescents (age range: 4-18; mean age: 10.4 years) were randomized; 4087 were vaccinated, and a subset of 301 children participated in the immunogenicity analysis. Children were randomized to receive either 30 microgram of LD vaccine (N = 3063) or placebo (N = 1024) on a 0, 1, 12-month schedule. Safety assessments evaluated both solicited (local: redness, swelling, and pain; general: fever, headache, fatigue, arthralgia, and rash) and unsolicited adverse events. Serum specimens were collected at month 0 or month 2, and months 6, 12, and 13., Results: Solicited reactogenicity data revealed a higher incidence of local injection site reactions and general symptoms (fever, headache, fatigue, and arthralgia) in vaccine than placebo recipients. The majority of events were limited in duration (mean: 2-3 days) and were mild to moderate in severity. The total IgG anti-OspA geometric mean titer (GMT) in the pediatric vaccine recipients at month 13 was as good as and statistically higher than the GMT in the adult cohort at month 13 (27 485 enzyme-linked immunosorbent assay units [EL.U]/mL vs 8216 EL.U /mL). All of the pediatric vaccine recipients attained a level of antibody concentration >/=1400 EL.U/mL (proposed seroprotective level) compared with 90% of adults attaining levels >/=1400 EL.U/mL in the efficacy trial., Conclusions: LD vaccine administered on a 0, 1, 12-month schedule generally is well tolerated and immunogenic in children 4 to 18 years of age. The safety profile consists of mild to moderate local injection site reactions and flu-like symptoms of limited duration and did not worsen with subsequent injections. IgG GMT at month 13 was threefold higher than the month 13 GMT obtained in the adult efficacy study. This higher immune response in children should provide protection against LD.

Lyme disease is a potentially serious and debilitating infection caused by Borrelia burgdorferi that is endemic in North America, Europe, and Asia. Personal protective and environmental measures have not significantly impacted its increasing incidence. An adjuvanted recombinant vaccine (LYMErix) has been approved in the United States for the prevention of Lyme disease in adults, and has demonstrated both safety and efficacy. A clinical trial of over 10000 adults showed 76% efficacy following the third dose of a 0, 1, 12 schedule. Accelerated schedules demonstrate equivalent levels of protective antibody. Up to 100% of children 2-14 years of age achieve seroprotective levels of antibody. Booster doses induced protective levels of antibody in more than 96% of recipients when administered at months 12 and 24. Only mild or moderate, transient vaccine-associated adverse events have been reported after immunization. The vaccine is a safe and effective method of preventing Lyme disease.

The development of an effective vaccine for Lyme disease represents a major advance in the control of the most prevalent vector-borne disease in the United States. It has a definite place in the total approach to control of this disease. Its use should be restricted to individuals who are at moderate to high risk of exposure to infected vector ticks. Vaccinated individuals should not be complacent about other personal protection measures, because the vaccine is not uniformly effective and protective antibody levels decay rapidly. Booster doses will be necessary, but the intervals have not yet been determined. There is a theoretical concern about the possible induction of inflammatory arthritis through an autoimmune mechanism, but there is no evidence that this condition has clinical relevance. The impact of the current lawsuits on vaccine recommendations and use remains to be determined. Continued surveillance for rare long-term side effects should address the medical risk issue. Alternative primary vaccine administration schedules are currently under study, and could lead to regimens permitting achievement of protective immunity in 6 months or less. Vaccine is not approved for use in children under the age of 15 years.

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