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Volume: 8
Issue: 03
Date: 27-Mar-00


Table of Contents:

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


Newsletter:

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                  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
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