Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Reexamination Certificate
1998-09-02
2001-01-09
Minnifield, Nita (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
C424S184100, C424S190100, C530S300000, C530S350000, C530S387100
Reexamination Certificate
active
06171589
ABSTRACT:
The present invention relates generally to peptides and polypeptides and their use in vaccine preparations. More particularly, the present invention is directed to a peptide or polypeptide or a derivative, homologue or analogue thereof which corresponds to, mimics, or cross-reacts with, B-cell or T-cell epitopes on polypeptides encoded by
Mycoplasma pneumoniae
and
M. genitalium
. Vaccine preparations comprising the peptides or polypeptides of the present invention are useful in protecting individuals against infections by species of the genus Mycoplasma.
Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
Bibliographic details of the publications referred to by author in this specification are collected at the end of the description.
Sequence identity numbers (SEQ ID Nos.) for the nucleotide and amino acid sequences referred to in the specification are defined after the bibliography.
The micro-organisms
Mycoplasma pneumoniae
is a pathogen of humans that typically colonises the upper respiratory tract.
Mycoplasma pneumoniae
moves along the cilia of the respiratory epithelium until in close association with the host cell to which it adheres. It disrupts the protein ciliary necklace at the base of the host cell cilia causing ciliostasis.
The threat the
M. pneumoniae
poses to children and sensitized adults is considerable.
Mycoplasma pneumoniae
is the primary cause of atypical pneumonia in young adults and children, although infected patients often present with symptoms similar to a persistent influenza infection. A study performed in the U.K. (Granstrom et al, 1994) has attributed 18% of the total number of cases of acquired pneumonia in the community, to
M. pneumoniae
infection. Periodically,
M. pneumoniae
is present in epidemic proportions in human communities. Previous exposure to the pathogen can result in hypersensitivity reactions upon reinfection (Cimolai et al, 1992).
Although only one in one thousand cases of
M. pneumoniae
infection result in pathology of the central nervous system (CNS), infection is associated with 5-10% of cases of neurological syndromes (Koskiniemi, 1993). Typical CNS manifestations associated with infection include encephalitis, meningitis and myelitis. Additional complications associated with
M. pneumoniae
infection include the presence of cold agglutinins and arthropathy (Cimolai et al, 1989). A report of Zagami et al. (1994) suggests that the neurological pathology of
M. pneumoniae
associated encephalitis results from a cell mediated response to shared
M. pneumoniae
antigens, or a local inflammatory response of the CNS due to the presence of
M. pneumoniae
in the CNS.
However, notwithstanding the endemic and serious nature of
M. pneumoniae
related disease, no means is available for the accurate and rapid diagnosis of
M. pneumoniae
infection, or for the prophylaxis of individuals exposed to infection. Accordingly, there is a clear need to develop agents useful in the diagnosis and prophylaxis of infection by mycoplasmas, in particular
M. pneumoniae.
Previous attempts to develop a suitable peptide vaccine against
M. pneumoniae
have been largely unsuccessful. For example, although hamsters immunised with
M. pneumoniae
may develop antibodies against the P1 protein of
M. pneumoniae
, the results, in terms of the degree of humoral immunity conferred by such immunisation, have been inconsistent and unpredictable (Yayoshi et al, 1992). In particular, hamsters inoculated with the P24-SII live vaccine, which contains the P1 protein but not the 85 kDa protein, were not protected against infection. The P24-SI live vaccine, containing the P1 protein and the 85 kDa protein, gave 50% protection against infection. The FH-P24 live vaccine, also containing both the P1 protein and the 85 kDa protein, gave 90% protection. The P24-SI and P24-SII vaccines are nitroso guanidine non-hemolysing mutants of FH-P24. Furthermore, no success has been obtained using the 43 kDa
M. pneumoniae
protein, which appears to enhance the severity of infection by this pathogen (Cimolai et al, 1992).
In work leading up to the present invention, the inventors sought to develop better and more effective vaccines and diagnostic agents for
M. pneumoniae
, by cloning.
M. pneumoniae
genes encoding highly immunogenic polypeptides and homologues and derivatives thereof. The recombinant polypeptides and derivatives, homologues or analogues thereof, provide the means to develop a range of diagnostic and prophylactic agents for Mycoplasma infection which were hitherto not available.
Accordingly, one aspect of the present invention is directed to an isolated or recombinant polypeptide or a derivative, homologue or analogue thereof wherein said polypeptide is obtainable from a species of Mycoplasma.
In one embodiment of the present invention, there is provided an isolated or recombinant polypeptide or derivative, homologue or analogue thereof wherein said polypeptide is obtainable from a species of Mycoplasma and has a predicted molecular weight of approximately 16 kDa.
Preferably, the isolated or recombinant polypeptide of the present invention or a derivative, homologue or analogue thereof is further obtainable from
Mycoplasma pneumoniae
or
M. genitalium
and
M. genitalium.
More preferably, said polypeptide further comprises an amino acid sequence substantially the same as the amino acid sequence set forth in SEQ ID NO:1 or SEQ ID NO:4, or is at least 70% similar to all or a part thereof.
In one particularly preferred embodiment, the isolated or recombinant polypeptide or a derivative, homologue or analogue thereof is characterised by any one or more of the following properties:
(I) it is obtainable from
Mycoplasma pneumoniae;
(ii) it has a predicted molecular weight of approximately 16 kDa; or
(iii) it comprises an amino acid sequence substantially as set forth in SEQ ID NO:1 or having at least 70% similarity to all or a part thereof.
Alternatively or in addition, the isolated or recombinant polypeptide or a derivative, homologue or analogue thereof is characterised by any one of the following properties:
(I) it is obtainable from
Mycoplasma genitalium;
(ii) it has a predicted molecular weight of approximately 16 kDa; or
(iii) it comprises an amino acid sequence substantially as set forth in SEQ ID NO:4 or having at least 70% similarity to all or a part thereof.
The homologous amino acid sequences set forth in SEQ ID Nos:1 and 4 are only 37.3% identical overall, as described in Example 21. Accordingly, the present invention further extends to any isolated Mycoplasma polypeptide which has properties of a surface polypeptide and is at least 35% identical to SEQ ID NO:1 or SEQ ID NO:4.
In an alternative embodiment of the present invention, there is provided an isolated polypeptide, or a derivative, homologue or analogue thereof wherein said polypeptide is obtainable from a species of Mycoplasma and wherein said polypeptide in its native form is a surface polypeptide which has adhesion properties.
Preferably, one embodiment is directed to an isolated polypeptide, or a derivative, homologue or analogue thereof wherein said polypeptide is obtainable from
Mycoplasma pneumoniae
, has a molecular weight of approximately 110 kDa determined by SDS/PAGE, or a predicted molecular weight of approximately 116 kDa and in its native form is a surface polypeptide which has adhesion properties.
For the present purposes, it will be understood that reference to the molecular weight of the subject polypeptide does not necessarily limit the invention, but is included especially for the purposes of nomenclature. Those skilled in the art are aware of the degree of precision associated with molecular weight estimates in respect of protein or polypeptide molecules and the fact that such estimates vary considerably
Browning Glenn Francis
Duffy Michael Francis
Walker Ian Douglas
Whithear Kevin George
Baskar Padma
Greenlee Winner and Sullivan PC
Minnifield Nita
The University of Melbourne
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