*********************************************************************** * The National Lyme Disease Network * * http://www.LymeNet.org/ * * LymeNet Newsletter * *********************************************************************** Publishing Lyme disease information on the Internet since 1993 Volume 8 / Number 03 / 27-MAR-2000 INDEX I. LYMENET: Aventis Pasteur Discontinues OspA Vaccine Effort, Focuses On Second Generation II. INFECT IMMUN: Occurrence of severe destructive lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. III. MOL DIAGN: Quantitative detection of Borrelia burgdorferi with a microtiter-based competitive polymerase chain reaction assay. IV. NAT MED: Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease V. ABOUT THE LYMENET NEWSLETTER =====*===== I. LYMENET: Aventis Pasteur Discontinues OspA Vaccine Effort, Focuses On Second Generation ---------------------------------------------------------------- Date: February 15, 2000 Source: Aventis S.A. SWIFTWATER, Pa. -- Aventis Pasteur, the human vaccines business of Aventis S.A., said today that the company has decided to channel its resources into the development of a second-generation, multiple-antigen vaccine for the prevention of Lyme disease. As a result, the development program for a first-generation vaccine, called ImuLyme(TM), will be discontinued, and, instead, channeled into the effort to develop an improved multiple-antigen product. In 1999, Aventis Pasteur announced it had entered into a license agreement with MedImmune, Inc., for worldwide rights to technology related to decorin binding protein (DbpA), which is found on the organism that causes Lyme disease. Terms of the agreement were not disclosed. ``We believe that a multiple-antigen Lyme disease vaccine would offer significant advantages over the first-generation vaccine currently on the market,'' said David J. Williams, president and COO of Aventis Pasteur. ``Our intention is to use DbpA in combination with our existing rights to various other surface protein technologies, for the development of an improved vaccine,'' he continued. He noted that ``Aventis Pasteur remains committed to research and development of a safe and effective vaccine to protect the millions of at-risk people who live under threat of this serious infectious disease.'' Aventis Pasteur operated under the Pasteur Merieux Connaught name until the creation of Aventis. Aventis was launched on December 15, 1999 through the merger of Hoechst AG and Rhone-Poulenc SA. =====*===== II. INFECT IMMUN: Occurrence of severe destructive lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi. ------------------------------------------------------------------- AUTHORS: Croke CL, Munson EL, Lovrich SD, Christopherson JA, Remington MC, England DM, Callister SM, Schell RF ORGANIZATION: Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, Wisconsin 53706, USA. REFERENCE: Infect Immun 2000 Feb;68(2):658-63 ABSTRACT: Arthritis is a frequent and major complication of infection with Borrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 microg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 microg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferi sensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferi sensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans. =====*===== III. MOL DIAGN: Quantitative detection of Borrelia burgdorferi with a microtiter-based competitive polymerase chain reaction assay. --------------------------------------------------------------------- AUTHORS: Germer J, Ryckmann B, Moro M, Hofmeister E, Barthold SW Bockenstedt L, Persing DH ORGANIZATION: Division of Experimental Pathology, Mayo Clinic, Rochester, Minnesota, USA. REFERENCE: Mol Diagn 1999 Sep;4(3):185-93 ABSTRACT: BACKGROUND: The current understanding of the inflammation associated with Lyme disease directly involves infection caused by Borrelia burgdorferi within specific target tissues, accompanied by a significant host immunologic component driving the inflammatory process. The measurement of spirochetal tissue burden may thus be useful for studying animal models of Lyme disease pathogenesis. Widely available methods based on the culture of spirochetes from tissues do not provide quantitative information. METHODS: We developed and evaluated a quantitative-competitive polymerase chain reaction assay based on amplification of the B. burgdorferi flagellin gene. The assay makes use of a competitive internal standard and a commercially available enzyme-linked immunosorbent assay detection kit. RESULTS AND CONCLUSION: The assay clearly discriminated between infected and uninfected mouse tissues, and an accurate quantitation range of 500 to 20,000 spirochetes per milligram of tissue was obtained. C3H mice were shown to harbor greater amounts of spirochetal genomic DNA than BALB/c mice. Normalization of samples by tissue weight and genomic DNA content both provided acceptable results. These data indicate this assay can be used to provide reliable and meaningful measurements of spirochetal infectious burden, which will be extremely useful for the study of Lyme disease pathogenesis in the murine model. =====*===== IV. NAT MED: Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease -------------------------------------------------------------- AUTHORS: Hemmer B, Gran B, Zhao Y, Marques A, Pascal J, Tzou A Kondo T, Cortese I, Bielekova B, Straus SE, McFarland HF Houghten R, Simon R, Pinilla C, Martin R ORGANIZATION: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5B-16, 10 Center DR MSC 1400, Bethesda, Maryland 20892-1400, USA. REFERENCE: Nat Med 1999 Dec;5(12):1375-82 ABSTRACT: Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases. =====*===== V. ABOUT THE LYMENET NEWSLETTER ----------------------------------------------------------------------- For the most current information on LymeNet subscriptions, contributions, and other sources of information on Lyme disease, please refer to: http://newsletter.lymenet.org ----------------------------------------------------------------------- To unsubscribe from the LymeNet newsletter, send a message to: listserv@lehigh.edu On the first line of the message, write: unsub lymenet-l ----------------------------------------------------------------------- LymeNet - The Internet Lyme Disease Information Source ----------------------------------------------------------------------- Editor-in-Chief: Marc C. Gabriel Contributing Editors: Carl Brenner John Setel O'Donnell Frank Demarest <76116.2065@CompuServe.com> Advisors: Carol-Jane Stolow, Director William S. Stolow, President The Lyme Disease Network of New Jersey ----------------------------------------------------------------------- WHEN COMMENTS ARE PRESENTED WITH AN ATTRIBUTION, THEY DO NOT NECESSARILY REPRESENT THE OPINIONS/ANALYSES OF THE EDITORS. ----------------------------------------------------------------------- THIS NEWSLETTER MAY BE REPRODUCED AND/OR POSTED ON BULLETIN BOARDS FREELY AS LONG AS IT IS NOT MODIFIED OR ABRIDGED IN ANY WAY. ----------------------------------------------------------------------- SEND ALL BUG REPORTS TO a229@Lehigh.EDU -----------------------------------------------------------------------