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WO1996007910A1 - Substance pour le diagnostic de l'infection par le chlamydia - Google Patents

Substance pour le diagnostic de l'infection par le chlamydia Download PDF

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Publication number
WO1996007910A1
WO1996007910A1 PCT/JP1995/001755 JP9501755W WO9607910A1 WO 1996007910 A1 WO1996007910 A1 WO 1996007910A1 JP 9501755 W JP9501755 W JP 9501755W WO 9607910 A1 WO9607910 A1 WO 9607910A1
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thr
ala
peptide
chlamydia
gly
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PCT/JP1995/001755
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English (en)
Japanese (ja)
Inventor
Kohsuke Kino
Toshifumi Oshima
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Meiji Milk Products Company Limited
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Priority to AU33550/95A priority Critical patent/AU3355095A/en
Publication of WO1996007910A1 publication Critical patent/WO1996007910A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/295—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Chlamydiales (O)

Definitions

  • the present invention relates to a diagnostic agent for Chlamydia infection. More specifically, the present invention relates to a diagnostic agent that is effective for the selective diagnosis of patients infected with Chla mydia trachomatis or Chlamydia pneumoniae.
  • Chlamydia infects humans and causes various diseases. Chlamydia is a wounded intracellular parasitic bacterium that has a unique ⁇ ring with morphological changes. When it is outside the host cell, it is resistant to the outside world and is infectious but has no metabolic activity.It has a form of elementary body (EB) with a diameter of 30 O nm and enters the host cell. It is non-infectious but metabolically active, with a morphological change to a fragile reticulate body (RB) with a diameter of about 450-: L50O nm. RB repeats two-way growth in host cells and assembles into cells to form inclusion bodies. Then, the RB changes its form from RB to EB via an intermediate form (intermediate form), and when the host cell is broken down, EB is released to the outside world.
  • EB elementary body
  • RB fragile reticulate body
  • C. trachomatis is known as a pathogen that causes granulomatous conjunctivitis (trachoma), sexually transmitted diseases (STDs), and infertility.
  • STDs cause urethritis, Sugao-maruitis, and prostatitis in men, but only in women It has been reported that childhood appendicitis (tubulitis), bone, and peritonitis may develop, causing infertility.
  • tubulitis tubulitis
  • peritonitis may develop, causing infertility.
  • vertical transmission to newborns via the birth canal during delivery may cause the newborns to develop conjunctivitis or pneumonia.
  • trachoma The incidence of trachoma is more common in developing countries, and according to a WHO study in 1981, 500 million people in developing countries suffer from trachoma per year, of which 10 million are due to this. I'm blind.
  • STDs caused by trachomatis are common in developed countries.For example, in the United States, 400,000 women a year are at risk of infertility due to peritonitis due to C. trachomatis infection and the risk of infertility. C. trachomatis has been called as one of the STDs to prevent its infection from a public health standpoint.
  • trachoma was widespread for some time after World War II as an infectious disease of C. trach omatis, but recently STD has been added as in the United States, and early detection of infection has become an important issue. ing.
  • C. pneumoniae has recently been identified as a species of chlamydia22, and subsequent studies have shown that antibody prevalence is high (several tens of percent) even in healthy people, indicating that it is a common infectious microorganism in humans. found.
  • the pathogenicity of acute respiratory harbor infections has been reported, and it is reported that more than 10% of pneumonia cases are pathogenic microorganisms. Under such circumstances, as in C. trachomatis, an early diagnosis method for infection is required.
  • an antigen assay for detecting Chlamydia cells or their constituents using a specimen (scratch specimen) or urine collected from the affected area by abrasion, and a serum sample using Chlamydia antibodies There is an antibody measurement method to detect.
  • Antigen testing methods include the isolation culture method, fluorescent antibody method, enzyme antibody method, DNA Diagnostic methods have been developed.
  • the scraped sample is inoculated into He229 or McCoy cells, cultured, fixed and stained, and the presence or absence of Chlamydia inclusions is determined under a microscope. This is the most reliable diagnostic method,
  • a sample is reacted with an anti-chlamydia antibody labeled with an enzyme (/ 3-D-galactosidase or peroxidase), and 4 MU G (4-methylujn belliferyl- ⁇ -D-galactopyranoside) is labeled with the labeled enzyme. Or ⁇ ⁇ (3, 3 ', 5, o-tetramethylbenzidine).
  • an enzyme / 3-D-galactosidase or peroxidase
  • 4 MU G 4-methylujn belliferyl- ⁇ -D-galactopyranoside
  • ⁇ ⁇ 3, 3 ', 5, o-tetramethylbenzidine.
  • LPS lipopolysaccharide
  • chlamydia ribosomal RNA in a sample or plasmid DNA universal to chlamydia and a DNA probe complementary thereto are hybridized, and the probe that contributes to hybrid formation is detected by chemiluminescence or color development. Things.
  • the enzyme immunoassay is performed using chlamydia-infected cells, purified EB, and EB outer membrane protein as antigens. This method is quick and simple, and can process a large number of samples. However, since none of the antigens used is species-specific, there is a problem that cross-reaction may occur between Chlamydia species. ⁇ In the X stamp lotting method, EBs are subjected to electrophoresis, and then the electrophoretic proteins are transferred to a membrane.
  • a sample serum is reacted with the membrane, reacted with an enzyme-labeled anti-human immunoglobulin antibody, and then colored with TMB or the like, and the presence or absence of a band having high species-specific chlamydia is determined.
  • the Chlamydia infection diagnosis method other than the isolation culture method and the DNA diagnosis method in the antigen test method uses a Chlamydia specific antibody or antigen and binds it to the Chlamydia specific antigen or antibody in the sample, respectively. It is a fundamental principle. However, any of the conventionally used antigens or antibodies have cross-reactivity between species due to insufficient species specificity. In particular, when diagnosing C. trachomatis infection, false positives are likely to occur because pneumoniae is universally transmitted to humans. Problem. Therefore, the development of a new diagnostic drug that solves this cross-reactivity has been required.
  • an object of the present invention is to provide a species-specific diagnostic agent for Chlamydia ⁇ : to increase the antigen specificity of each of C. trachomatis and C, pneumoniae, or to increase the antigen specificity of an antibody. To provide a diagnostic for Chlamydia infection.
  • a B cell epitope specific for Chlamydia is searched for, and a diagnostic drug for Chlamydia infectious disease containing a peptide containing the same or an antibody against the peptide is contained.
  • the present inventors thought that it would suffice to produce a diagnostic agent for Chlamydia infection.
  • MOMP major outer membrane protein
  • VD as a site having low amino acid sequence homology between trachomatis and C. pneumoniae
  • VD I to VD IV and VD I focusing on VD as a site involved in antigenicity.
  • the peptides containing trachomatis species-specific B-cell epitopes include peptides near the VD I of C. trachomatis and VD IV of C. tracho matis, and species-specific C. pneumoniae. B-cell episode! ⁇
  • VD IV of C. pneumoniae was found, respectively. That is, as the peptide containing the species-specific B cell epitope of C. trachomatis !, a peptide having an amino acid sequence of the following (1) to (15):
  • the peptide containing the species-specific B cell epitope of C pneumoniae is a peptide having the following amino acid sequence of (16):
  • the peptides (1) to (14) correspond to the C. trachomatis strains B, D, L, L1 wL2, r rest, Crtt, A3 ⁇ 4 :, H, I, J, respectively.
  • the sequence of the peptide in the VDIV region of the C. trachomatis Ba strain is the same as that of the B strain.
  • the present invention relates to C. trachomatis, in which the peptide represented by any of the amino acid sequences (1) to (15) and the peptide represented by the amino acid sequence or a peptide immunologically equivalent to the peptide represented by the amino acid sequence are used. And any of the peptides represented by the amino acid sequences of (1) to (15) and peptides that are immunologically equivalent to the peptides represented by the amino acid sequences. The deviated ones are linked together, and for C. pneumoniae,
  • a peptide represented by the amino acid sequence of (16) and / or a peptide immunologically equivalent to the peptide represented by the amino acid sequence; and a peptide represented by the amino acid sequence of (16) and / or Peptides that are immunologically equivalent to the indicated peptide are linked together (hereinafter sometimes collectively referred to as a specific antigen), or an antibody against the specific antigen (hereinafter sometimes referred to as a specific antibody). It is used as a diagnostic for Chlamydia infection.
  • the “ ⁇ immunologically equivalent peptide” refers to the peptide represented by the amino acid sequence of (1) to (16) above, wherein one or more amino acid residues are deleted and / or substituted and Z Or a peptide having an inserted and / or added amino acid sequence, which reacts immunologically equivalent to the original unmodified peptide to the serum of a patient with Chlamydia trachomatis infection positive or serum of a patient with Chlamydia pneumoniae infection positive Refers to those indicated, especially those with a cut-off index of 1.50 or more as measured by enzyme-linked immunosorbent assay for infection-positive patient sera.
  • the 15 serotypes of C. trachomatis were classified into groups B (B, Ba, D, E, L1, L2) and C (C A, H, I, J, K, and L3 strains) and an intermediate group (F and G strains). Therefore, as shown in Example 3, by selecting peptides in one or more strains of the VD IV region from each of these groups and using a mixture of these as an antigen, the detection sensitivity of the antibody test can be increased. Can be increased.
  • a combination of peptides in the VD IV region of one or more strains of each of the group B, group C and intermediate group is particularly preferably used in the present invention.
  • the peptide in the VDI region which Jones et al. Considered to be reactive with the serum of a patient infected with C. trachomatis, was not reactive in the experiments of the present inventors. This is because non-specific reactions were judged to be positive because the patients were white and Japanese, or because they did not have a negative control (reactivity with healthy human serum) experimental system. Possible causes are possible, but unknown.
  • Chlamydia species other than C. trachomatis and C. pneumoniae eg, C. psittaci
  • species-specific B cell epitopes are searched for from among the EB outer membrane components of the species. It is possible to produce a diagnostic agent for Chlamydia infection comprising a peptide containing the same, or a diagnostic agent for Chlamydia infection comprising an antibody against the peptide.
  • the production of a diagnostic agent for Chlamydia infectious disease using the peptides (1) to (16) is described below.
  • the antigens used in the antibody test are as follows. Diagnostic agents for trachomatis infection include peptides represented by any one of the amino acid sequences of (1) to (15) or a combination of these peptides, and species-specific B-cell epitopes of Z or C. trachomatis. A partial peptide of the peptide represented by any one of the amino acid sequences (1) to (15), including a partial peptide, or a combination of these partial peptides is used.
  • the diagnostic agent for C. pneumoniae infection use is made of the peptide represented by the amino acid sequence of (16) or a partial peptide thereof containing a species-specific B cell epitope of pneumoniae.
  • the antibodies used in the antigen test are as follows. The diagnostic agent for C.
  • trachomatis infectious disease includes a peptide having the amino acid sequence of any one of (1) to (15) or a portion having a species-specific B cell epitope of C. trachomatis (1).
  • the peptide represented by the amino acid sequence of (16) or the partial peptide containing the portion having the species-specific B-cell epitope of pneumoniae can be obtained by using a heron, guinea pig, Use a peptide antibody obtained by immunizing a mouse, goat, sheep or the like.
  • the peptides (1) to (16) or their partial peptides are all low in molecular weight and have no immunogenicity as they are, so that serum albumin, KLH ( The peptide is bound to a carrier protein such as keyhole limpet hemocyanin) as a hapten, and a sufficient amount of a peptide to induce an immune response is injected into the animal, and the antibody is recovered from the serum of the animal.
  • mice are immunized with a hybrid and a sodopeptide that combines the binding motif of the mouse major histocompatibility complex and a peptide to obtain the target antibody.
  • a method of making the body work can also be used.
  • the antibody any of a polyclonal antibody and a monoclonal antibody can be used, but in the case of using an antibody targeting a specific epitope as in the present invention, it is more preferable to use a monoclonal antibody.
  • the specific antigen or specific antibody of the present invention can be used for any immunoassay such as enzyme immunoassay, fluorescence immunoassay, radioimmunoassay, chemiluminescence immunoassay, particle agglutination, immunochromatography, and the like.
  • the specific antigen or the specific antibody of the present invention is used by binding to a carrier for immobilization or a labeled substance.
  • a carrier for immobilization include polystyrene resin, acrylamide resin, latex particles, and gelatin particles.
  • the labeling substance an enzyme (Peruokishida Ichize, P- D-galactosidase and the like; an enzyme immune ⁇ method), fluorescence substances (FITC like; fluorescence immunoassay), radioisotopes (such as 1 ZS I; Rajioi ⁇ Noatsusi) , Chemiluminescent substances (such as luminol; chemiluminescent Imnoassay), and colloidal gold.
  • FITC fluorescence immunoassay
  • radioisotopes such as 1 ZS I; Rajioi ⁇ Noatsusi
  • Chemiluminescent substances such as luminol; chemiluminescent Imnoassay
  • colloidal gold When the specific antigen or the specific antibody is bound to the immobilizing carrier or the labeling substance, a spacer structure may be interposed between them by a covalent bond or the like.
  • CT # 1 VDI neighborhood peptide; L 2 strain
  • the above peptides were synthesized with Shimadzu Peptide Synthesizer P SSM8. Was. Synthesis was carried out by the Fmoc method, and the peptide was biotinylated by reacting NHS-biotin (Pierce) with the amino terminal of the synthesized peptide. The synthesized peptide was desorbed from the solid phase, deprotected for protecting groups, purified to a purity of 95% or more with a reversed-phase column of HP LC, and subjected to amino acid analysis to confirm the synthesized product. The enzyme immunoassay was performed as follows.
  • bovine serum albumin Phosphate-impregnated physiological saline (PH7.3) was added to 200 ⁇ l Zwell, and the mixture was allowed to stand overnight at 4 to bind the synthetic peptide to a biotinylated plate or a streptavidinized plate.
  • Serum samples were added at 50 i 1 / well and reacted at 37 T! For 1 hour. Serum diluent was used as a blank. Serum was used for 10 healthy patients with C. trachomatis infection (cut off index (cut off index) of 1.00 or more in antibody measurement using Cellopalizer Chlamydia IgGG manufactured by Savyon Diagnostics) and health.
  • Serum from 10 humans (cut off index for the same diagnostic drug manufactured by the company and the cut off index was 1.00 drops) was diluted 64 times and used. After the reaction, the plate is washed 5 times with a washing solution, and then diluted 5000 times with a serum diluent. A human IgG antibody (manufactured by Dako) was added to 50 ⁇ l of Zwell, and reacted with 37 for 1 hour. After the reaction, the plate was washed 5 times with a washing solution, and 100 ⁇ l / well of TMB (manufactured by Savyon Diagnostics) diluted 10-fold with purified water was added, and the mixture was reacted at room temperature for 15 minutes. After the reaction, 100 # 1 Zwell was added with 2 N ruic acid, and the absorbance at 450 nm was measured with a microplate reader using a blank as a control.
  • TMB manufactured by Savyon Diagnostics
  • Table 1 shows the results. Since no reaction was observed in all serum samples for CT # 3 peptide, the relative value to the absorbance of other peptides was calculated by setting the absorbance for CT # 3 peptide to 1.00, and calculated as 1.50. The above was determined to be positive. As a result, in CT # 2 to CT # 5 (VDI, VD ⁇ and VD ⁇ ), no positive serum sample was observed, and the positive match rate with ⁇ Cellophilizer Chlamydia IgG '' was 0%. .
  • the peptide synthesized from the VD IV region (CT # 6 to CT # 8) showed a positive match rate of 40, 0% to 70.0%, and the peptide near the VD I, CT # 1, also showed a positive 20.0% The concordance rate was high (negative concordance rate was 100.0%, indicating good concordance rate).
  • the VD IV region shows up to 70% positive concordance, indicating that this region is a fairly common epitope among patients.
  • the VD IV region has an amino acid sequence of about 30 residues, but CT # 6 is the first half including the N-terminal, and D # 7 is the second half including the (: terminal (CT # 6 And CT # 7 overlap each other in the central part of the VD IV region.)
  • CT # 6 is the first half including the N-terminal
  • D # 7 is the second half including the (: terminal (CT # 6 And CT # 7 overlap each other in the central part of the VD IV region.)
  • CT # 6 is the first half including the N-terminal
  • D # 7 is the second half including the (: terminal (CT # 6 And CT # 7 overlap each other in the central part of the VD IV region.)
  • CT # 6 is the first half including the N-terminal
  • D # 7 is the second half including the (: terminal (CT # 6 And CT # 7 overlap each other in the central part of the VD IV region.
  • Example 2 (Species-specific reactivity of VD IV and VDI neighboring peptides) The results of Example 1 revealed that two or more B cell epitopes were present in the VD IV region. In an effort to increase the efficiency, we synthesized about 30 residues of peptide C. pneumoniae. C. trachomatis strain C and C. trachoaatis strain E across the VD IV region. In addition, CT # 1 described in Example 1 was also synthesized. The synthesis, biotinylation, purification and confirmation of the synthesized product of these peptides were performed in the same manner as in Example 1. The amino acid sequence and peptide name of the peptide synthesized in this example are as follows.
  • CT # 1 (peptide near VDI; trachomatis L 2 strain)
  • Trp_Asn-Pro_Ser Leu-Leu-Gly-Asn-Ala-Thr-Ala-Leu-Ser-Thr-Thr-Asp- Ser-Phe-Ser
  • Enzyme immunoassay was performed in the same manner as in Example 1, except that the binding of the synthetic peptide to the biotinylated plate or the streptavidinized plate was performed for each of these peptides alone, as well as for CT #. 1, Peptide mixture of 3 kinds of peptides of CT # 9 and CT # 10 (Hereinafter referred to as CT mixture).
  • CT mixture Peptide mixture of 3 kinds of peptides of CT # 9 and CT # 10 (Hereinafter referred to as CT mixture).
  • CT mixture Peptide mixture of 3 kinds of peptides of CT # 9 and CT # 10
  • ⁇ Cerroparaizer Chlamydia IgG is a positive serum
  • CT (1) serogroup Chlamydia IgG-negative serogroup
  • CT # 1 CT with the absorbance of the negative control as 1.00
  • the CT (1) serogroup did not react with any of the CT peptides and showed good agreement with r cellophylizer chlamydia IgGj. It is unknown whether the serum samples in this group also have antibodies against C. pneumoniae, but all three serum samples showed a negative reaction to the CP peptide.
  • a combination of peptides in the VD IV region of multiple serotypes of C. trachomatis, or a combination of peptides near the VD I may be used as a diagnostic agent for Chlamydia infection with higher reactivity. It is possible.
  • the VD IV region was a peptide of the entire VD IV region or a combination of these peptides or a species-specific C. trachomatis in the L2 strain, E strain, and C strain of C. trachomatis. High partial-reactivity of these partial peptides, including those with a typical B-cell epitope, was confirmed.
  • other strains of C. trachomatis B strain, Ba strain, D strain
  • Strains, L1, F, G, A, H, I, J, K and L3 strains peptides in all regions of VD IV or species-specific B cell peptides of C.
  • trachomatis These partial peptides, including those with a loop, also have high homology to each other In view of the above, it is considered that it has the same type-specific reactivity as the L2 strain, E strain, or C strain. Therefore, peptides of the entire VD IV of a strain other than L2, E, or C strains, or a combination of such peptides, and those containing a portion having a Z- or C. trachomatis species-specific B-cell epitope It is also possible to develop a highly reactive diagnostic agent for Chlamydia infectious disease using a partial peptide or a combination of these partial peptides.
  • the 15 serotypes of C. trachomatis were compared in the sequence of the VD IV region and found to be group B (strains B, Ba, D, E, L1, L2), group C (strain C, A Strains, H, I, J, K, and L3 strains) and an intermediate group (F and G strains). Therefore, it is considered that by selecting one or more peptides of the VD IV region from each of these groups and using a mixture thereof as an antigen, the detection sensitivity of the antibody test can be further improved. .
  • the peptide of the VD IV region of one strain (L2 strain) was used as an antigen
  • one or more of the peptides of the VD IV region of one or more strains were selected from each of these groups, and a mixture thereof ( L2 strains, C strains, E strains, and G strains) were used as antigens, and a comparison of the positive rate agreement rate with the Western blotting test result was performed.
  • the enzyme immunoassay was performed in the same manner as in Example 1. >> Spontaneous / negative was judged as positive if the OD " 0 value of the specimen was divided by the cut-off value (cut-off index; COI) was 1.0 or more, and negative if not 1.0.
  • the test by the Western blotting method was performed as follows.
  • the antigen (EB of L2 strain) diluted 10-fold with the blotting buffer was applied to a 4 to 12% gradient gel (TEFCO) in an amount of 180 ⁇ l and subjected to electrophoresis with one 15 AZ sheet.
  • the electrophoretic protein was transferred to the membrane at 180 A / sheet using a blotting unit (manufactured by TEFCO).
  • TEFCO 4 to 12% gradient gel
  • the membrane was washed twice with PBS, dried and stored at 4. Then PBS containing 5% wZv skim milk For 2 hours, washed twice with PBS containing 0.05% w / v Tween 20, and then set on a screen plotter (manufactured by SAN PLATEC).
  • Sample serum diluted 100-fold with PBS containing 5% wv skim milk was applied at 2501 per lane and allowed to react at room temperature for 2 hours. Remove the membrane from the screen plotter. 1 After washing 5 times with PBS containing 6020, and reacting for 1 hour in 2 Oml of peroxidase-labeled anti-human IgG V chain antibody (manufactured by TAGO) diluted 2000-fold with PBS containing 1% wZv BSA. Washing was performed 5 times. Finally, the cells were immersed in 5 OmM Tris-HC 1 P H7.2 containing 0.05% 3,3 'diaminobenzidine and 0.01% 11 2 ⁇ 2 to determine the species specificity of MOM P. The band (about 40KD) was checked for color development.
  • the present invention it is possible to provide a diagnostic agent for species-specific Chlamydia infection, and thus, it is possible to more reliably and easily infect C. trachomat is or C. pneumoniae, which has been difficult to confirm until now. It is possible to make a diagnosis immediately.

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Abstract

La présente invention concerne une substance pour le diagnostic de l'infection par le chlamydia. Cette substance comprend un peptide contenant un épitope spécifique du Chlamydia trachomatis et un épitope spécifique du Chlamydia pneumoniæ, ou un anticorps réagissant contre ce peptide. Cette substance étant spécifique des espèces, elle permet de diagnostiquer plus précisément et plus facilement l'infection par le chlamydia trachomatis et le chlamydia pneumoniæ pour laquelle le diagnostic précis a présenté jusqu'ici des difficultés.
PCT/JP1995/001755 1994-09-02 1995-09-04 Substance pour le diagnostic de l'infection par le chlamydia WO1996007910A1 (fr)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998057981A2 (fr) * 1997-06-19 1998-12-23 Savyon Diagnostics Ltd. Peptides specifiques de c. pneumoniae et leur utilisation dans les dosages diagnostiques
WO1999000414A1 (fr) * 1997-06-19 1999-01-07 Savyon Diagnostics Ltd. Peptides specifiques a chlamydia trachomatis et leur utilisation dans des methodes diagnostiques
JP2001286295A (ja) * 2000-01-31 2001-10-16 Asahi Kasei Corp クラミジア・トラコマチス検出用抗体
JP2010268800A (ja) * 1998-07-31 2010-12-02 Asahi Kasei Corp 微生物検出用抗体
JP2012006968A (ja) * 2000-01-31 2012-01-12 Asahi Kasei Corp マイコプラズマ・ニューモニア検出用抗体
JP2012017334A (ja) * 2000-01-31 2012-01-26 Asahi Kasei Corp クラミジア・ニューモニア検出用抗体
WO2013008743A1 (fr) * 2011-07-11 2013-01-17 富士レビオ株式会社 Antigène de chlamydophila pneumoniae et son utilisation

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JPH0686679A (ja) * 1990-03-23 1994-03-29 F Hoffmann La Roche Ag プラズモジウム・スポロゾイド抗原
JPH06205693A (ja) * 1992-08-05 1994-07-26 Behringwerke Ag 顆粒球結合性抗体構築物、それらの製造方法および使用
WO1995011998A1 (fr) * 1993-10-26 1995-05-04 United Biomedical, Inc. Bibliotheques structurees d'antigenes de synthese utilisables a des fins de diagnostic, de vaccin et de therapie

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Publication number Priority date Publication date Assignee Title
EP0192033A2 (fr) * 1985-01-14 1986-08-27 Chiron Corporation Protéine principale de la membrane externe de Chlamydia
JPH0686679A (ja) * 1990-03-23 1994-03-29 F Hoffmann La Roche Ag プラズモジウム・スポロゾイド抗原
JPH06205693A (ja) * 1992-08-05 1994-07-26 Behringwerke Ag 顆粒球結合性抗体構築物、それらの製造方法および使用
WO1995011998A1 (fr) * 1993-10-26 1995-05-04 United Biomedical, Inc. Bibliotheques structurees d'antigenes de synthese utilisables a des fins de diagnostic, de vaccin et de therapie

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WO1998057981A2 (fr) * 1997-06-19 1998-12-23 Savyon Diagnostics Ltd. Peptides specifiques de c. pneumoniae et leur utilisation dans les dosages diagnostiques
WO1999000414A1 (fr) * 1997-06-19 1999-01-07 Savyon Diagnostics Ltd. Peptides specifiques a chlamydia trachomatis et leur utilisation dans des methodes diagnostiques
WO1998057981A3 (fr) * 1997-06-19 1999-03-11 Savyon Diagnostics Ltd Peptides specifiques de c. pneumoniae et leur utilisation dans les dosages diagnostiques
US6699678B1 (en) 1997-06-19 2004-03-02 Savyon Diagnostics Ltd. Chlamydia trachomatis specific peptides and their use in diagnostic assays
JP2010268800A (ja) * 1998-07-31 2010-12-02 Asahi Kasei Corp 微生物検出用抗体
JP5219057B2 (ja) * 1998-07-31 2013-06-26 旭化成株式会社 微生物検出用抗体
JP2001286295A (ja) * 2000-01-31 2001-10-16 Asahi Kasei Corp クラミジア・トラコマチス検出用抗体
JP2012006968A (ja) * 2000-01-31 2012-01-12 Asahi Kasei Corp マイコプラズマ・ニューモニア検出用抗体
JP2012017334A (ja) * 2000-01-31 2012-01-26 Asahi Kasei Corp クラミジア・ニューモニア検出用抗体
JP5331285B2 (ja) * 2000-01-31 2013-10-30 旭化成株式会社 マイコプラズマ・ニューモニア検出用抗体
JP5331284B2 (ja) * 2000-01-31 2013-10-30 旭化成株式会社 クラミジア・ニューモニア検出用抗体
WO2013008743A1 (fr) * 2011-07-11 2013-01-17 富士レビオ株式会社 Antigène de chlamydophila pneumoniae et son utilisation

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