Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1994-07-05
2000-09-05
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
4241841, 4241851, 4241901, 4242031, 435 732, 435 693, 435 712, 436543, 530350, 530359, 530403, 530806, 530820, 530825, A61K 3900, A61K 3902, A61K 39116, G01N 33554
Patent
active
061139149
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel antigens, to methods for their production, to compositions containing them and to their use in the prevention, treatment and diagnosis of Lyme Disease in humans and other animals. In particular the present invention discloses novel serotypes/genotypes of the outer surface protein (Osp A) from the spirochete Borrelia burgdorferi, the causative agent of Lyme disease, and vaccine and diagnostic reagents based on B. burgdorferi of more than one subgroup.
Lyme disease in humans is a chronic progressive disease caused by B burgdorferi, which is transmitted to humans mainly by Ixodes ticks. The disease attacks many organs, notably the skin, heart, liver, central and peripheral nervous system, kidneys as well as the musculoskeletal system.
Lyme disease itself is the most common vector borne infection in the USA and has been reported in every continent except Antarctica.
A number of groups have isolated and proposed the major surface protein (Osp A) of B. burgdorferi, as being a potential vaccine candidate for use against Lyme disease. For example, International patent application published under WO90/04411 (SIMBICOM) discloses the cloning and expression of an Osp A protein derived from B. burgdorferi B31 and its use as a vaccine, M. M. Simon and colleagues have cloned and expressed Osp A from B. burgdorferi ZS7 (European Patent Application No. 90117943.2 published under No. 0418 827), and demonstrated its protective capacity to induce antibodies in passively immunised SCID mice (PNAS: 87 1990, 3768-3772). Flavell and colleagues (Science (1991) 250 p553-556) have cloned and expressed the gene for Osp A from B. burgdorferi, N40 and have demonstrated its protective efficacy in C3H/He mice.
All isolates of B. burgdorferi identified above appear to be closely related. However we have now identified six subgroups of B. burgdorferi by analysing 55 spirochete isolates from different geographical areas and sources with series of immunological, biochemical and molecular genetic techniques. The finding of different subgroups of B. burgdorferi isolates have important implications for both effective vaccination and diagnosis of Lyme disease. Since ELISA diagnostic assays directed against a strain of which species N40 is a member would not or only partially cross react with species from other subgroups. Equally a vaccine based on only one Osp A for example from N40 would not provide optimal protection against B. burgdorferi from a different subgroup.
The present inventors have identified five additional subgroups of B. burgdorferi based on their Southern blotting and PCR amplification of Osp A sequences, and differences in the amino acid and nucleic acid sequences themselves and also in reactivity against monoclonal antibodies to Osp A proteins.
The surprising discovery that B. burgdorferi exhibits such heterogeneity has important implications for vaccines against, and diagnostics reagents for the detection of, Lyme disease, since vaccines or diagnostic based on an Osp A from one group of B. burgdorferi may not detect or protect against infection of B. burgdorferi from a second group. Indeed the present inventors have shown that whereas protection can be afforded by anti Osp A antibodies generated by recombinant Osp A or viable or killed organisms within a group of closely related strains, no or only partial, protection is observed if challenge is made with an organism from a different group.
A first subtype having representative ZS7, B31, N40 is referred to herein as group I (alternative nomenclature refers to group I strains as group A).
A second subgroup hereinafter group II (alternatively known as group B) is herein disclosed and is exemplified by the species ZQ1. This species has been deposited at the DSM Deutsche Sammlung von Mikroorganismen Und Zellkulturen of Mascheroderweg 91B D-3300 Braunschweig on Jul. 11, 1991 and given the accession No. DSM6606. This group is distinct in a number of ways from group I.
Firstly, plasmid analysis of strain ZQ1 when compared with representatives f
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Kramer Michael
Lobet Yves
Schaible Ulrich
Simon Markus
Wallich Reinhard
Dustman Wayne J.
Housel James C.
King William T.
Kinzig Charles M.
Ryan V.
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