OspE-Related, OspF-Related, and Elp Lipoproteins Are Immunogenic in Baboons Experimentally Infected withBorrelia burgdorferiand in Human Lyme Disease Patients

Abstract

Presently, the rhesus macaque is the only nonhuman primate animal model utilized for the study of Lyme disease. While this animal model closely mimics human disease, rhesus macaques can harbor the herpes B virus, which is often lethal to humans; macaques also do not express the full complement of immunoglobulin G (IgG) subclasses found in humans. Conversely, baboons contain the full complement of IgG subclasses and do not harbor the herpes B virus. For these reasons, baboons have been increasingly utilized as the basis for models of infectious diseases and studies assessing the safety and immunogenicity of new vaccines. Here we analyzed the capability of baboons to become infected with Borrelia burgdorferi, the agent of Lyme disease. Combined culture and PCR analyses of tick-and syringe-infected animals indicated that baboons are a sufficient host for B. burgdorferi. Analysis of the antibody responses in infected baboons over a 48-week period revealed that antibodies are generated early during infection against many borrelial antigens, including the various OspE, OspF, and Elp paralogs that are encoded on the ubiquitous 32-kb circular plasmids (cp32s). By using the baboon sera generated by experimental infection it was determined that a combination of two cp32-encoded lipoproteins, OspE and ElpB1, resulted in highly specific and sensitive detection of B. burgdorferi infection. An expanded analysis, which included 39 different human Lyme disease patients, revealed that a combination of the OspE and ElpB1 lipoproteins could be the basis for a new serodiagnostic assay for Lyme disease. Importantly, this novel serodiagnostic test would be useful independent of prior OspA vaccination status.Lyme disease, the most common arthropod-borne disease in North America (49,50,70), is a multisystem disorder characterized by dermatologic, cardiac, neurologic, and arthritic manifestations (68, 69). Lyme disease pathogenesis and Borrelia burgdorferi infectivity have been studied in numerous animal models; however, the disease manifestations observed vary widely among host species (9). The murine model of Lyme disease has been the most intensively investigated and is presently the preferred animal model for Lyme disease research. The mouse model has allowed researchers to gain valuable insight into the effects of various components of the immune system in relation to Lyme disease pathogenesis (10, 13, 57, 64, 68, 69). However, there are drawbacks to the mouse model of Lyme disease. For instance, the mouse immune system and how it responds to B. burgdorferi infection can differ from the human immune response to this organism. Furthermore, not all disease manifestations observed in humans also are observed in mice, especially the erythema migrans and neurologic symptoms typically associated with Lyme disease (74).Presently, the rhesus macaque (Macaca mulatta) provides the closest animal model to human Lyme disease. Infection of these animals with B. burgdorferi results in an almost complete spectrum of human disease and the various ...

Putative Coiled-Coil Structural Elements of the BBA68 Protein of Lyme Disease Spirochetes Are Required for Formation of Its Factor H Binding Site

“…The OspE protein of the Lyme disease spirochetes serves as a case in point. While this protein is antigenic and immunogenic (12,29,33), it does not elicit a protective Ab response (30), and the Ab response to the protein is to restricted domains (29). It is our hypothesis that modification of these proteins so that they no longer bind factor H will lead to the development of a less restricted, and potentially protective, Ab response.…”

Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal–tick infection cycle

“…Transcripts from erp genes have been detected in various tissues of infected laboratory animals, including non-human primates, throughout the course of disseminated and persistent infection . B. burgdorferi-infected mice mount rapid antibody responses to Erp proteins Akins et al, 1995;Suk et al, 1995;Wallich et al, 1995;Stevenson et al, 1998;Miller et al, 2000b;Hefty et al, 2001Hefty et al, , 2002McDowell et al, 2001). Erp-directed antibodies persist at high levels and periodically increase during prolonged infection, suggesting sustained exposure (and re-exposure) to Erp proteins throughout chronic infection .…”

The emergence of Lyme disease

“…In addition, the spirochete binds mammalian plasminogen and its activators, present in the blood meal, which facilitates spreading of the organism within the tick (24). Within the salivary gland, OspC expression predominates, but some organisms express only OspE and OspF; OspA and OspB are absent (25). After transmission of the spirochete, human Lyme disease generally occurs in stages, with remissions and exacerbations and different clinical manifestations at each stage (4).…”