C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

Jobe, Dean A.; Lovrich, Steven D.; Schell, Ronald F.; Callister, Steven M.

doi:10.1128/cdli.10.4.573-578.2003

Cited by 29 publications

(38 citation statements)

References 37 publications

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“…In contrast, OspA is rapidly downregulated upon spirochete entry into the mammal [19,20]. Immunization with OspC is protective but the protection range is narrow [14][15][16][21][22][23][24][25][26][27][28][29]. In an analysis of B. burgdorferi sensu stricto, 21 different OspC phylogenetic types were described and designated by letter (A-U) [30,31].…”

Section: Introductionmentioning

confidence: 99%

Construction and analysis of variants of a polyvalent Lyme disease vaccine: Approaches for improving the immune response to chimeric vaccinogens

Earnhart

Marconi

2007

Vaccine

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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.

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Section: Introductionmentioning

confidence: 99%

Construction and analysis of variants of a polyvalent Lyme disease vaccine: Approaches for improving the immune response to chimeric vaccinogens

Earnhart

Marconi

2007

Vaccine

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“…This protein is expressed in the tick midgut and salivary gland (24) and also during the early stages of infection in the mammalian host (31). Moreover, this protein is susceptible to anti-OspC borreliacidal antibodies, especially those specific for the C terminus (12,21). In addition, researchers showed recently that a bivalent bacterin that induced high levels of both anti-OspA and anti-OspC borreliacidal antibodies provided complete protection from Lyme disease spirochetes shortly after immunization (14).…”

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confidence: 99%

One-Year Duration of Immunity Induced by Vaccination with a Canine Lyme Disease Bacterin

LaFleur

Callister

Dant

et al. 2010

Clin Vaccine Immunol

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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. burgdorferiinfected 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 OspCproducing B. burgdorferi 50772 provided enhanced protection.

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“…Because there are differences in the lipoproteins expressed by in vitro grown and host-adapted B. burgdorferi (15), it was important to determine whether the reduced borreliacidal activity observed against in vitro grown B. burgdorferi correlated with a reduced antibody response against host-adapted B. burgdorferi proteins. OspC is abundantly expressed in host-adapted B. burgdorferi (22), and anti-OspC antibodies have been shown to be, in many cases, the most important borreliacidal antibody (36). Therefore, we looked at the antibody response to recombinant OspC.…”

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confidence: 99%

β2 Integrins Control the Severity of Murine Lyme Carditis

2005

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Infection of C57BL/6 (B6) mice with the Lyme disease spirochete Borrelia burgdorferi can result in development of arthritis and carditis. B. burgdorferi induces expression of ␤2/CD18 integrins, adhesion molecules that mediate the firm adhesion of leukocytes to the endothelium necessary for cellular extravasation during inflammation. The important role of ␤2/CD18 integrins during extravasation suggests that these molecules play a role in the development of Lyme arthritis and carditis. The dependency of these inflammatory processes on the ␤2 integrins was investigated in CD18 hypomorph mice, which express low levels of CD18. The results indicate that CD18 deficiency did not abrogate development of Lyme arthritis or carditis. Moreover, it resulted in increased severity of Lyme carditis. B. burgdorferi-infected CD18 hypomorph mice showed an increased macrophage infiltration of the heart, while they produced lower levels of borreliacidal anti-B. burgdorferi antibodies compared to wild-type mice. In accordance with these results, we demonstrate that dendritic cells from CD18 hypomorph mice secrete higher levels of monocyte/macrophage chemoattractant protein 1 (MCP-1/CCL2) in response to B. burgdorferi. Similarly, we show by real-time PCR that B. burgdorferi-infected hearts from CD18 hypomorph mice express increased levels of MCP-1 RNA compared to wild-type mice. Overall, our results indicate that ␤2 integrin deficiency does not abrogate B. burgdorferi-induced inflammation; rather, it results in increased recruitment of macrophages into the B. burgdorferi-infected heart, likely due to the increased expression of MCP-1 in this tissue. Thus, ␤2 integrins may play a regulatory role in B. burgdorferiinduced inflammation beyond mediating adhesion of leukocytes to the endothelium.

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C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

Cited by 29 publications

References 37 publications

Construction and analysis of variants of a polyvalent Lyme disease vaccine: Approaches for improving the immune response to chimeric vaccinogens

Construction and analysis of variants of a polyvalent Lyme disease vaccine: Approaches for improving the immune response to chimeric vaccinogens

One-Year Duration of Immunity Induced by Vaccination with a Canine Lyme Disease Bacterin

β2 Integrins Control the Severity of Murine Lyme Carditis

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