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Erol Fikrig - One of the best experts on this subject based on the ideXlab platform.
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an open label nonrandomized single center prospective extension clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer surface protein a ospa Lyme Disease Vaccine
Clinical Therapeutics, 2003Co-Authors: Robert T. Schoen, Charles Buscarino, Terry Deshefylonghi, Christian Vanhoecke, Erol FikrigAbstract:Abstract 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 ⩾1400 EL.U/mL. Adverse events (AEs) were recorded by the study volunteers on diary cards.
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Lyme Disease Vaccine
2003Co-Authors: Janine Evans, Erol FikrigAbstract:Lyme Disease occurs throughout the world. Most cases of Lyme borreliosis are reported from temperate regions and coincide with the distribution of the principal vector, ticks of the Ixodes ricinus complex, including I. ricinus, which is found in most of Europe; Ixodes persulcatus, which is found in eastern Europe and Asia; Ixodes pacificus, found in the northwestern United States; and Ixodes scapularis is found in the eastern and central United States.1 (Fig. 1)
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hyporesponsiveness to vaccination with borrelia burgdorferi ospa in humans and in tlr1 and tlr2 deficient mice
Nature Medicine, 2002Co-Authors: Lena Alexopoulou, Robert T. Schoen, Venetta Thomas, Markus Schnare, Yves Lobet, Juan Anguita, Ruslan Medzhitov, Erol Fikrig, Richard A FlavellAbstract:The Lyme Disease Vaccine is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of Vaccine recipients develop substantial titers of antibodies against OspA. Here, we identified seven individuals with very low antibody titers after vaccination (low responders). The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2. TLRs activate innate responses to pathogens, and TLR2 recognizes lipoproteins and peptidoglycan (PGN). After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA. Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA. These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
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the Lyme Disease Vaccine takes its toll
Vector-borne and Zoonotic Diseases, 2002Co-Authors: Venetta Thomas, Erol FikrigAbstract:Vaccination with Borrelia burgdorferi outer surface protein (Osp) A can induce a protective response against Lyme Disease and serves as a model to understand the generation of protective immune responses against the spirochete. The innate response to pathogens is activated by specific Toll-like receptors (TLRs) that recognize distinct pathogen-associated molecular patterns. TLR2 is of particular interest for B. burgdorferi research because TLR2 recognizes several pathogen-associated molecular patterns, including lipoproteins. TLR2 may form heterodimers with TLR6 to identify diacylated lipoproteins, while TLR2 works in concert with TLR1 to recognize triacylated lipoproteins such as OspA. We will discuss the role of TLR1/2 in the development of responses to OspA in TLR1-and TLR2-deficient mice, and in selected individuals that received the OspA Vaccine. While > 95% of human OspA-based Lyme Disease Vaccine recipients develop OspA antibodies, a very small group of individuals did not develop detectable humoral responses against OspA. We demonstrated that this hyporesponsiveness to OspA vaccination was associated with decreased cell surface expression of TLR1. Moreover, TLR1- and TLR2-deficient mice did not develop significant levels of OspA antibodies following vaccination with OspA, providing a correlation with human hyporesponsiveness to OspA. These data suggest that defects in the TLR1/2 signaling pathway are associated with an impaired ability to generate antibodies following immunization with OspA lipoprotein.
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attachment of borrelia burgdorferi within ixodes scapularis mediated by outer surface protein a
Journal of Clinical Investigation, 2000Co-Authors: Utpal Pal, Yves Lobet, Juan Anguita, A M De Silva, Durland Fish, John F Anderson, Ruth R Montgomery, Erol FikrigAbstract:Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme Disease Vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.
Richard T Marconi - One of the best experts on this subject based on the ideXlab platform.
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vanguard crLyme a next generation Lyme Disease Vaccine that prevents b burgdorferi infection in dogs
Vaccine: X, 2020Co-Authors: Richard T Marconi, David Garciatapia, Jacquelien Hoevers, Nicole Honsberger, Vickie L King, Dianne Ritter, Denise J Schwahn, Leroy Swearingin, Angela Weber, Teresa M C WinklerAbstract:Lyme Disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick (Ixodes) transmitted spirochete, Borreliella burgdorferi. Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme Disease Vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit Vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the Vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme Disease.
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disulfide mediated oligomer formation in borrelia burgdorferi outer surface protein c a critical virulence factor and potential Lyme Disease Vaccine candidate
Clinical and Vaccine Immunology, 2011Co-Authors: Christopher G Earnhart, Delacy V L Rhodes, Richard T MarconiAbstract:Borrelia burgdorferi OspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution among B. burgdorferi sensu lato strains and high antigenicity, it is being explored for the development of a next-generation Lyme Disease Vaccine. An understanding of the surface presentation of OspC will facilitate efforts to maximize its potential as a Vaccine candidate. OspC forms homodimers at the cell surface, and it has been hypothesized that it may also form oligomeric arrays. Here, we employ site-directed mutagenesis to test the hypothesis that interdimeric disulfide bonds at cysteine 130 (C130) mediate oligomerization. B. burgdorferi B31 ospC was replaced with a C130A substitution mutant to yield strain B31::ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required for in vivo function, as B31::ospC(C130A) retained infectivity and disseminated normally. The total IgG response and the induced isotype pattern were similar between mice infected with untransformed B31 and those infected with the B31::ospC(C130A) strain. These data indicate that the immune response to OspC is not significantly altered by formation of OspC oligomers, a finding that has significant implications in Lyme Disease Vaccine design.
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an octavalent Lyme Disease Vaccine induces antibodies that recognize all incorporated ospc type specific sequences
Human Vaccines, 2007Co-Authors: Christopher G Earnhart, Richard T MarconiAbstract:Lyme Disease is the most common vector-borne Disease in North America and Europe and, if untreated, has significant arthritic, cardiac, dermatological and neurological sequelae. There is no currently available human Lyme Disease Vaccine. Outer surface protein C, because of its antigenicity, protective ability, and expression characteristics has emerged as a promising second generation Vaccine candidate; however, significant sequence heterogeneity has impeded its development. Analyses of OspC sequences have revealed the existence of stable phylogenetic clusters or types, and that the type-defining sequence variation occurs within defined domains of the protein. Recent data indicating that immunodominant, and potentially protective OspC epitopes are located in these hypervariable regions has allowed development of a tetravalent, epitope-based, chimeric Vaccine. In this report, we have extended that previously described tetravalent construct to include four additional OspC types. We demonstrate that the construct is highly immunogenic, and elicits type-specific antibodies that recognize each of the eight incorporated OspC type-specific epitopes. Antibody raised to the octavalent construct readily binds to the surface of strains expressing each component OspC type, indicating that the incorporated epitopes are presented on the surface of intact cells. In addition, the construct elicits antibody isotypes associated with complement-dependent bactericidal activity. These results represent an important step forward in the design of a broadly protective polyvalent OspC-based Lyme Disease Vaccine.
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ospc phylogenetic analyses support the feasibility of a broadly protective polyvalent chimeric Lyme Disease Vaccine
Clinical and Vaccine Immunology, 2007Co-Authors: Christopher G Earnhart, Richard T MarconiAbstract:Using available Borrelia outer surface protein C (OspC) sequences, a phylogenetic analysis was undertaken to delineate the number of antigenic domains required for inclusion in a broadly protective, chimeric, OspC-based Lyme Disease Vaccine. The data indicate that approximately 34 would be required and that an OspC-based vaccinogen is feasible.
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construction and analysis of variants of a polyvalent Lyme Disease Vaccine approaches for improving the immune response to chimeric vaccinogens
Vaccine, 2007Co-Authors: Christopher G Earnhart, Richard T MarconiAbstract:There is currently no Lyme Disease Vaccine commercially available for use in humans. Outer surface protein C (OspC) of the Borrelia has been widely investigated as a potential vaccinogen. At least 38 OspC types have been defined. While the antibody response to OspC is protective, the range of protection is narrow due to the localization of protective epitopes within OspC type-specific domains. To develop a broadly protective Vaccine, we previously constructed a tetravalent chimeric vaccinogen containing epitopes from OspC types A, B, K, and D. While this construct elicited bactericidal antibody against strains bearing each of the four OspC types, its solubility was low, and decreasing IgG titer to epitopes near the C-terminus of the construct was observed. In this report, construct solubility and immunogenicity were increased by dialysis against an Arg/Glu buffer. We also demonstrate the immunogenicity of the construct in alum. To further optimize epitope-specific immune responses, several constructs were generated with differing epitope organization or with putative C-terminal protective motifs. Analyses of murine antibody titers and isotype profiles induced by these constructs revealed that while the C-terminal tags did not enhance antibody titer, specific epitope reorganization and reiteration did. These analyses provide important information that can be exploited in the development of chimeric vaccinogens in general.
Gary P. Wormser - One of the best experts on this subject based on the ideXlab platform.
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single tier testing with the c6 peptide elisa kit compared with two tier testing for Lyme Disease
Diagnostic Microbiology and Infectious Disease, 2013Co-Authors: Gary P. Wormser, Martin E Schriefer, Andrew E Levin, Adriana Marques, Barbara J B Johnson, Maria E Aguerorosenfeld, Robert B. Nadelman, John Nowakowski, Allen C Steere, Stephen J DumlerAbstract:Abstract For the diagnosis of Lyme Disease, the 2-tier serologic testing protocol for Lyme Disease has a number of shortcomings including low sensitivity in early Disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7–71.1) and 35.2% (95% CI 30.6–40.1), respectively ( P P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme Disease Vaccine recipients were found to be 98.9% and 99.5%, respectively ( P
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single tier testing with the c6 peptide elisa kit compared with two tier testing for Lyme Disease
Diagnostic Microbiology and Infectious Disease, 2013Co-Authors: Gary P. Wormser, Martin E Schriefer, Andrew E Levin, Adriana Marques, Barbara J B Johnson, Maria E Aguerorosenfeld, Robert B. Nadelman, John Nowakowski, Allen C Steere, Stephen J DumlerAbstract:For the diagnosis of Lyme Disease, the 2-tier serologic testing protocol for Lyme Disease has a number of shortcomings including low sensitivity in early Disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme Disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme Disease Vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme Disease with comparable sensitivity in later manifestations of Lyme Disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice.
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modulation of lymphocyte proliferative responses by a canine Lyme Disease Vaccine of recombinant outer surface protein a ospa
Fems Immunology and Medical Microbiology, 2000Co-Authors: J W Chiao, P Villalon, Ira Schwartz, Gary P. WormserAbstract:The modulation of human lymphocyte proliferative responses was demonstrated with a recombinant outer surface protein A (OspA) Vaccine preparation for the prevention of Borrelia burgdorferi infection. After exposure to either the unaltered Vaccine preparation or OspA prepared in saline, normal lymphocyte responses to the mitogens concanavalin A, phytohemagglutinin-M or pokeweed mitogen, or the antigen BCG were consistently reduced. Whole cell extracts of B. burgdorferi also modulated immune responses but required a much greater quantity of protein than needed for the OspA preparation. The magnitude of modulation was directly dependent on the quantity of OspA. OspA interferes with the response of lymphocytes to proliferative stimuli including a blocking of cell cycle phase progression. Future studies designed to delete the particular region or component of the OspA molecule responsible for this effect may lead to improved Vaccine preparations.
Robert T. Schoen - One of the best experts on this subject based on the ideXlab platform.
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asymptomatic infection with borrelia burgdorferi
Clinical Infectious Diseases, 2003Co-Authors: Allen C Steere, Robert T. Schoen, Vijay K. Sikand, John NowakowskiAbstract: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.
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an open label nonrandomized single center prospective extension clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer surface protein a ospa Lyme Disease Vaccine
Clinical Therapeutics, 2003Co-Authors: Robert T. Schoen, Charles Buscarino, Terry Deshefylonghi, Christian Vanhoecke, Erol FikrigAbstract:Abstract 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 ⩾1400 EL.U/mL. Adverse events (AEs) were recorded by the study volunteers on diary cards.
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hyporesponsiveness to vaccination with borrelia burgdorferi ospa in humans and in tlr1 and tlr2 deficient mice
Nature Medicine, 2002Co-Authors: Lena Alexopoulou, Robert T. Schoen, Venetta Thomas, Markus Schnare, Yves Lobet, Juan Anguita, Ruslan Medzhitov, Erol Fikrig, Richard A FlavellAbstract:The Lyme Disease Vaccine is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of Vaccine recipients develop substantial titers of antibodies against OspA. Here, we identified seven individuals with very low antibody titers after vaccination (low responders). The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2. TLRs activate innate responses to pathogens, and TLR2 recognizes lipoproteins and peptidoglycan (PGN). After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA. Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA. These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
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the Lyme Disease Vaccine conception development and implementation
Annals of Internal Medicine, 2000Co-Authors: Wendy Todaro Thanassi, Robert T. SchoenAbstract:In the past 20 years, remarkable strides have been made toward understanding and preventing Lyme Disease in humans. In December 1998, the U.S. Food and Drug Administration approved a recombinant outer surface protein A Vaccine against Lyme Disease (Lymerix, SmithKline Beecham, Philadelphia, Pennsylvania). The Vaccine, which is derived from a lipidated outer surface protein of the causative spirochete Borrelia burgdorferi, is important because it may decrease the morbidity and financial costs associated with Lyme Disease. Its mechanism is unique because it works inside the tick vector itself, preventing the human from becoming infected.
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Safety and immunogenicity profile of a recombinant outer-surface protein a Lyme Disease Vaccine: Clinical trial of a 3-dose schedule at 0, 1, and 2 months
Clinical Therapeutics, 2000Co-Authors: Robert T. Schoen, Vijay K. Sikand, Michael C. Caldwell, Christian Van-hoecke, Marc Gillet, Charles Buscarino, Dennis L. ParentiAbstract:Objectives: This study compared the tolerability of a Lyme Disease Vaccine administered intramuscularly at 0 and 1 months with that of a Vaccine administered at 0, 1, and 2 months to determine (1) whether adding a third dose of Vaccine 1 month after the second would affect the safety profile, and (2) whether a shortened vaccination schedule of 0, 1, and 2 months would provide an immune response similar to that obtained with Vaccine administered at 0, 1, and 12 months. Background: An efficacy trial of a Lyme Disease Vaccine had demonstrated safety and efficacy against definite (clinically manifested and laboratory-confirmed) Lyme Disease after 3 doses at 0, 1, and 12 months and resulted in 90% of subjects having titers ≥1400 enzyme-linked immunosorbent assay units (EL.U)/mL (the proposed seroprotective level for 1 tick season). Methods: This multicenter, open-label, prospective, randomized study assessed the safety and efficacy of different doses of a recombinant outer-surface protein A (OspA) Vaccine in 956 volunteers aged 17 to 72 years from 3 Lyme Disease-endemic sites. Blood samples were collected at months 0, 2, 3, 12, and 13 to assess total immunoglobulin-G anti-OspA titers. Results: Most adverse events were transient and mild to moderate. The geometric mean antibody titer increased 2.8-fold from month 2 (1786 EL.U/mL to 4842 EL.U/mL), and ~90% of the volunteers had a titer ≥1400 and 99% had a titer ≥400 EL.U/mL (the minimum seroprotective level at any given time) after the third dose. An antibody kinetics model predicts that protection would last for a typical tick-transmission season. Conclusions: In volunteers aged 17 to 72 years, 3 doses of Vaccine administered in 2 months was well tolerated, more immunogenic than 2 doses, and provided a higher probability of protection before exposure or travel to Lyme Disease-endemic areas.
Yves Lobet - One of the best experts on this subject based on the ideXlab platform.
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hyporesponsiveness to vaccination with borrelia burgdorferi ospa in humans and in tlr1 and tlr2 deficient mice
Nature Medicine, 2002Co-Authors: Lena Alexopoulou, Robert T. Schoen, Venetta Thomas, Markus Schnare, Yves Lobet, Juan Anguita, Ruslan Medzhitov, Erol Fikrig, Richard A FlavellAbstract:The Lyme Disease Vaccine is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of Vaccine recipients develop substantial titers of antibodies against OspA. Here, we identified seven individuals with very low antibody titers after vaccination (low responders). The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2. TLRs activate innate responses to pathogens, and TLR2 recognizes lipoproteins and peptidoglycan (PGN). After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA. Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA. These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
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attachment of borrelia burgdorferi within ixodes scapularis mediated by outer surface protein a
Journal of Clinical Investigation, 2000Co-Authors: Utpal Pal, Yves Lobet, Juan Anguita, A M De Silva, Durland Fish, John F Anderson, Ruth R Montgomery, Erol FikrigAbstract:Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme Disease Vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.
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efficacy of human Lyme Disease Vaccine formulations in a mouse model
The Journal of Infectious Diseases, 1995Co-Authors: Sam R Telford, Yves Lobet, Richard A Flavell, Stephen W. Barthold, F S Kantor, Andrew Spielman, Erol FikrigAbstract:Although immunization with recombinant outer surface protein A (OspA) appears to protect mice against infection by the agent of Lyme Disease, all reported experiments have involved formulations that would not be suitable for use in humans or have not used realistic challenges. This study was designed to determine whether Vaccines prepared and used in a phase I human trial, including one currently being used for a phase II trial in sites with endemic Borrelia burgdorferi, conferred protection in the C3H/HeJ mouse model. The challenge was ticks collected from a major site of the trial. None of the vaccinated mice became infected or developed Disease, whereas 60% of unvaccinated mice became infected. Spirochetes were destroyed within the guts of virtually all recovered challenge ticks. These preparations of recombinant OspA effectively induced immunity to protect mice from Lyme Disease when bitten by ticks collected from a field trial site.
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the Lyme Disease Vaccine candidate outer surface protein a ospa in a formulation compatible with human use protects mice against natural tick transmission of b burgdorferi
Vaccine, 1995Co-Authors: William T Golde, Joseph Piesman, Thomas R Burkot, Marc C Dolan, Carine Capiau, Pierre Hauser, Guy Dequesne, Yves LobetAbstract:Development of a Vaccine for the Lyme Disease spirochete, Borrelia burgdorferi, has focused on the bacterial lipoprotein, major outer surface protein A (OspA). With few exceptions, testing of OspA Vaccines in animal models has involved challenge with needle inoculation of cultured spirochetes. Recombinant OspA proteins from two OspA divergent strains of B. burgdorferi were tested for their Vaccine potential in three different strains of mice challenged with laboratory reared ticks with a high rate of B. burgdorferi infection. All formulations of the B. burgdorferi sensu stricto derived OspA Vaccine protected all strains of mice when challenged by ticks infected with an OspA homologous strain of the spirochete, whereas heterologous OspA from B. afzelii did not protect. Furthermore, ticks feeding on protected mice had reduced OspA levels compared to unvaccinated controls.
