title: Antibody Response to Lyme Disease Spirochetes in the Context of VlsE-Mediated Immune Evasion.
abstract: Lyme disease (LD), the most prevalent tick-borne illness in North America, is caused by Borrelia burgdorferi The long-term survival of B. burgdorferi spirochetes in the mammalian host is achieved though VlsE-mediated antigenic variation. It is mathematically predicted that a highly variable surface antigen prolongs bacterial infection sufficiently to exhaust the immune response directed toward invariant surface antigens. If the prediction is correct, it is expected that the antibody response to B. burgdorferi invariant antigens will become nonprotective as B. burgdorferi infection progresses. To test this assumption, changes in the protective efficacy of the immune response to B. burgdorferi surface antigens were monitored via a superinfection model over the course of 70 days. B. burgdorferi-infected mice were subjected to secondary challenge by heterologous B. burgdorferi at different time points postinfection (p.i.). When the infected mice were superinfected with a VlsE-deficient clone (ΔVlsE) at day 28 p.i., the active anti-B. burgdorferi immune response did not prevent ΔVlsE-induced spirochetemia. In contrast, most mice blocked culture-detectable spirochetemia induced by wild-type B. burgdorferi (WT), indicating that VlsE was likely the primary target of the antibody response. As the B. burgdorferi infection further progressed, however, reversed outcomes were observed. At day 70 p.i. the host immune response to non-VlsE antigens became sufficiently potent to clear spirochetemia induced by ΔVlsE and yet failed to prevent WT-induced spirochetemia. To test if any significant changes in the anti-B. burgdorferi antibody repertoire accounted for the observed outcomes, global profiles of antibody specificities were determined. However, comparison of mimotopes revealed no major difference between day 28 and day 70 antibody repertoires.
authors: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA arogovskyy@cvm.tamu.edu.
authors: Artem S
authors: AS
authors: Rogovskyy
authors: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
authors: David C
authors: DC
authors: Gillis
authors: Department of Cancer Genetics, Rosewell Park Cancer Institute, Buffalo, New York, USA.
authors: Yurij
authors: Y
authors: Ionov
authors: Department of Computer Science, Georgia State University, Atlanta, Georgia, USA.
authors: Ekaterina
authors: E
authors: Gerasimov
authors: Department of Computer Science, Georgia State University, Atlanta, Georgia, USA.
authors: Alex
authors: A
authors: Zelikovsky
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000940:Antigenic Variation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology; D057131:Immune Evasion / Q000276:immunology*; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009656:North America; D013144:Spirochaetales / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D008074:Lipoproteins; C105546:VlsE protein, Borrelia burgdorferi
keywords: Borrelia burgdorferi; Lyme disease; VlsE; antibody repertoire; antibody response; mimotopes; protective efficacy; suppression