Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Reexamination Certificate
1998-12-23
2001-07-10
Salimi, Ali R. (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
C424S204100, C435S005000, C435S007920, C435S007930, C530S300000, C536S023720
Reexamination Certificate
active
06258363
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to immunoreactive peptides that are homologous with the region of amino acid positions 12 to 235 of the
varicella zoster
virus protein VP26, to nucleic acids which encode these peptides and to the use of the peptides and nucleic acids for diagnosing an infection with
varicella zoster
virus.
BACKGROUND OF THE INVENTION
In accordance with the classification of the International Committee on Taxonomy of Viruses (ICTV), Van Zoute Vin (VZV) is assigned to the Herpesviridae family. In 75% of cases, primary infections take place not later than the age of 15 and usually take an asymptomatic course. By contrast, infection of adults who have not previously had any contact with the virus and in persons who are naturally or therapeutically immunosuppressed can be associated with severe symptoms. Infection of the fetus also leads to severe symptoms since the virus is able to cross the placenta, and maternal antibodies afford no protection at this time. Following primary infection, the virus persists throughout life in sensory ganglia. After reactivation, the VZV spreads over the peripheral nerves in sensory ganglia and then gives rise to herpes zoster.
Seventy open reading frames (ORF), including the open reading frames for the known glycoproteins gpI (ORF 68), gpII (ORF 31), gpIII (ORF 37), gpIV (ORF 67), gpV (ORF 14) and gpVI (ORF 60), can be deduced from the sequence of the VZV genome, which has been completely elucidated and has a length of 124,884 bp (Dumas strain; (A. J. Davison & J. E. Scott (1986), J. Gen. Virol. 67, 1759-1816)). In each case, the amino acid sequence deduced from the nucleotide sequence displays differing degrees of homology with glycoproteins gE, gB, gH, gI, gC and gL of herpes simplex virus (HSV). However, there is nothing to suggest that the sequence homology can also imply a homologous function. The open reading frames of glycoproteins gpI, gpII, gpIII and gpV have been confirmed by means of molecular biology.
Only a few immunogenic VZV capsid proteins have been identified and characterized. D. R. Harper and C. Grose ((1989), J. Infect. Dis. 159, 444-451) describe immunoreactivity of the p32/p36 complex, which is assigned to the nucleocapsid. In addition, A. Vafai et al. ((1990), Virus Res. 15, 163-174) describe cross reactivity of human VZV-reactive sera, which recognize both the
varicella zoster
virus nucleocapsid protein and the HSV nucleocapsid protein. None of the authors propose an approach that would make it possible to use these antigens in diagnostic test methods.
There are a very large number of different serological methods for checking the level of VZV-specific immunity. Such methods range from radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), fluorescent-antibody membrane antigen assay (FAMA) and the immunofluorescence test (IFT) to complement fixation (CF). Most of those methods detect VZV-specific antibodies. Virus material which has been isolated following elaborate cultivation on human fibroblast cultures, and which has been prepared for diagnostic use in accordance with special methods, is frequently employed as the antigen.
The isolation of VZV antigens from infected fibroblasts is associated with the risk of infecting personnel who are entrusted with this task. In addition, preparation of antigens is very costly and time-consuming because the virus is not released from infected cells, and special purification methods are therefore required. When the antigen is to be used without prior purification for an immunochemical test, VZV-infected cells are disrupted by sonication, and the antigen is employed directly after dilution for coating microtitration plates, for example. In this method, primarily cell-specific antigens are bound to microtitration plate wells in addition to virus-specific antigens. Accordingly, cell-specific antigens can, particularly in association with certain diseases, for example autoimmune diseases, give rise to false-positive results and consequently to erroneous diagnoses. Other test methods that are based on use of purified viral glycoproteins, such a glycoprotein ELISA, require purification methods which, to a marked degree, are more elaborate and involve heavier losses, so that it has so far scarcely been possible to establish immunochemical diagnostic tests on a relatively large scale. Cross reactivity with HSV-specific antibodies, and, consequent, false-positive results, thus are frequently observed in glycoprotein ELISAs, due to pronounced homology that among glycoproteins of these á-herpesviruses.
SUMMARY OF THE INVENTION
In one embodiment of the invention, an immunoreactive peptide is provided which is homologous with the AA 12 to 235 region of VZV VP26. In another embodiment, a nucleic acid is provided which hybridizes under stringent conditions with a nucleic acid that encodes an immunoreactive peptide that is homologous with the AA 12 to 235 region of VZV VP26 wherein the peptide is recognized by antibodies directed against VZV but not recognized by antibodies which are directed against other herpes-viruses. In yet another embodiment, an immunochemical method is provided for detecting antibodies against VZV in a sample, comprising the step (a) contacting an immunoreactive peptide as described in claim
1
with the sample and (b) determining binding between antibody in the sample and the peptide. Another embodiment of the invention is a method for detecting VZV from a sample comprising the steps of contacting a nucleic acid as described above with the sample to allow hybridiztion of the nucleic acid, and determining the presence of nucleic acid hybrid formed. Yet another embodiment is a test kit for detecting antibodies against VZV, which comprises an immunoreactive peptide as described above or a nucleic acid which codes for such an immunoreactive peptide.
REFERENCES:
M.D. Davison et al., “Identification of genes encoding two capsid proteins (VP24 and VP26) of herpes simplex virus type 1”, J. Gen Virology, (1992), 73 pp. 2709-2713.
A.J. Davison et al., “J. Gen. Virol., vol. 67”,The Complete DNA Sequence of Varicella-Zoster Virus, pp. 1759-1816, (1986).
D.R. Harper et al., “The Journal of Infectious Diseases”, vol. 159 No. 3, IgM and IgG Responses to Varicella-Zoster Virus p32/p36 Complex After Chickenpox and Zoster, Congenital and Subclinical Infections, and Vaccination, pp. 444-451, (Mar. 1989).
A. Vafai et al., “Virus Research”, vol. 15, Antigenic cross-reaction between a varicella-zoster virus nucleocapsid protein encoded by gene 40 and a herpes simplex virus nucleocapsid protein, pp. 163-174 (1990).
Eickmann Markus
Gicklhorn Dorothee
Giesendorf Bernhard
Hauser Hans-Peter
Radsak Klaus
Dade Behring Marburg GmbH
Heller Ehrman White & McAuliffe LLP
Salimi Ali R.
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