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WO1987006469A1 - Anticorps monoclonaux et leur utilisation - Google Patents

Anticorps monoclonaux et leur utilisation Download PDF

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Publication number
WO1987006469A1
WO1987006469A1 PCT/GB1987/000279 GB8700279W WO8706469A1 WO 1987006469 A1 WO1987006469 A1 WO 1987006469A1 GB 8700279 W GB8700279 W GB 8700279W WO 8706469 A1 WO8706469 A1 WO 8706469A1
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WO
WIPO (PCT)
Prior art keywords
monoclonal antibody
legionella
antigen
antibody according
enzyme
Prior art date
Application number
PCT/GB1987/000279
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English (en)
Inventor
Bruce William Wright
Peter John Cox
Alice Margaret Noyes
Danny Widdows
Sandra Macfarlane
Cathleen Anne Saxby
Clive Graham Copley
Original Assignee
Technology Licence Company Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Technology Licence Company Limited filed Critical Technology Licence Company Limited
Publication of WO1987006469A1 publication Critical patent/WO1987006469A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/126—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Legionella (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This invention relates to monoclonal antibodies and their use. BACKGROUND OF THE INVENTION
  • Organisms (gram-negative) of the genus Legionella are found in water-cooling systems. They are implicated in Pontiac fever and legionaires disease.
  • Legionella pneumophila A species of the genus is Legionella pneumophila. There are perhaps 10 serotypes and various subspecies. Existing methods of detection of Legionella with high accuracy may be less than satisfactory in that they consume large amounts of expensive skilled labour and laboratory time, generally taking one and often several days before returning results.
  • the present invention provides novel monoclonal antibodies for use in accurately and rapidly diagnosing samples for the presence of Legionella antigens and/or organisms.
  • the present invention comprises monoclonal antibodies specific for an antigen of Legionella? in particular, the antigens of Legionella pneumophila (inc. subsp. SGI (particularly important) , SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20 etc.), as well as a monoclonal antibody broadly cross-reactive with an antigen for each species of the genus Legionella.
  • the invention also comprises labelled monoclonal antibodies for use in diagnosing the presence of the Legionella antigens, each comprising a monoclonal antibody against one of the above-mentioned antigens or to a particular species thereof and having linked thereto an appropriate label.
  • the label can be chosen from the group consisting of a radioactive isotope, enzyme, fluorescent compound, chemiluminescent compound, bioluminescent compound, ferromagnetic atom, or particle, or any other label.
  • the invention further comprises the process for diagnosing the presence of Legionella antigens or organisms in a specimen comprising contacting said specimen with the labelled monoclonal antibody in an appropriate immunoassay procedure.
  • the invention is also directed to a therapeutic composition
  • a therapeutic composition comprising a monoclonal antibody for an antigen of Legionella and a carrier or diluent, as well as kits containing at least one labelled monoclonal antibody to an antigen of Legionella.
  • the monoclonal antibodies of the present invention are prepared by fusing spleen cells, from a mammal which has been immunised against the particular Legionella antigen, with an appropriate myeloma cell line, preferably NSO (uncloned) , P3NS1-Ag4/1, or Sp2/0 Agl4.
  • an appropriate myeloma cell line preferably NSO (uncloned) , P3NS1-Ag4/1, or Sp2/0 Agl4.
  • the resultant product is then cultured in a standard HAT (hypoxanthine, aminopterin and thymidine) medium.
  • HAT hypoxanthine, aminopterin and thymidine
  • the immunised spleen cells may be derived from any mammal, such as primates, humans, rodents (i.e., mice. rats, rabbits) , bovines, ovines and canines, but the present invention will be described in connection with mice.
  • the mouse is first immunised by injection of the chosen Legionella antigen over a suitable period, e.g. of approximately eleven weeks. When the mouse shows sufficient antibody production against the antigen, as determined by conventional assay, it is given a booster injection of the appropriate Legionella antigen, and then killed so that the immunised spleen may be removed. The fusion can then be carried out utilising immunised spleen cells and an appropriate myeloma cell line.
  • the fused cells yielding an antibody which give a positive response to the presence of the particular Legionella antigen are removed and cloned utilising any of the standard methods.
  • the monoclonal antibodies from the clones are then tested against standard antigens to determine their specificity for the particular Legionella antigen.
  • the monoclonal antibody selected, which is specific for the particular Legionella antigen or species, is then bound to an appropriate label.
  • Amounts of antibody sufficient for labelling and subsequent commercial production are produced by the known techniques, such as by batch or continuous tissue culture or culture in vivo in mammals such as mice.
  • the monoclonal antibodies may be labelled with a multitude of different labels, such as enzymes, fluorescent compounds, luminescent compounds, radioactive compounds, ferromagnetic labels, and the like.
  • labels such as enzymes, fluorescent compounds, luminescent compounds, radioactive compounds, ferromagnetic labels, and the like.
  • the present invention will be described with reference to the use of an enzyme labelled monoclonal antibody.
  • Some of the enzymes utilised as labels are alkaline phosphatase, glucose oxidase, galactosidase, peroxidase, urease, and the like.
  • Such linkage with enzymes can be accomplished by any one of the conventional and known methods, such as the Staphylococcal Protein A method, the glutaraldehyde method, the benzoquinone method, or the periodate method.
  • EIA enzyme-linked immunosorbent assay
  • a non-labelled antigen and a specific antibody are combined with identical fluorescently-labelled antigen. Both labelled and non-labelled antigen compete for antibody binding sites.
  • the amount of labelled antigen bound to the antibody is dependent upon, and therefore a measurement of, the concentration of non-labelled antigen.
  • Examples of this particular type of fluorescent- immunoassay include heterogenous systems such as enzyme-linked fluorescent immunoassay, or homogeneous systems such as the substrate-labelled fluorescent immunoassay.
  • the most suitable fluorescent probe, and the one most widely used, is fluorescein. While fluorescein can be subject to considerable interference from scattering, sensitivity can be increased by the use of a fluorometer optimised for the probe utilised in the particular assay and in which the effect of scattering can be minimised.
  • Fluorescence polarisation In fluorescence polarisation, a labelled sample is excited with polarised light and the degree of polarisation of the emitted light is measured. As the antigen binds to the antibody its rotation slows down and the degree of polarisation increases. Fluorescence polarisation is simple, quick, and precise. However, at the present time its sensitivity is limited to the micromole per litre range and upper nano-mole per litre range with respect to antigens in biological samples.
  • Luminescence is the emission of light by an atom or molecule as an electron is transferred to the ground state from a higher energy state.
  • the free energy of a chemical reaction provides the energy required to produce an intermediate reaction or product in an electronically excited state. Subsequent decay back to the ground state is accompanied by emission of light.
  • Bioluminescence is the name given to a special form of chemiluminescence found in biological systems, in which a catalytic protein"or enzyme, such as luciferase, increases the efficiency of the luminescent reaction. The best known chemiluminescent substance is luminol.
  • a further aspect of the present invention is a therapeutic composition
  • a therapeutic composition comprising one or more of the monoclonal antibodies to the particular Legionella antigen or species, as well as a pharmacologically acceptable carrier or diluent.
  • Such compositions can be used to treat humans and/or animals afflicted with some form of Legionella infections and they are used in amounts effective to cure? an amount which will vary widely dependent upon the individual being treated and the severity of the infection.
  • One or more of the monoclonal antibodies can be assembled into a diagnostic kit for use in diagnosing for the presence of an antigen, antigens, or species of Legionella in various specimens. It is also possible to use the broadly cross-reactive monoclonal antibody which can identify the genus Legionella alone or as part of a kit containing antibodies that can identify other bacterial genera or species of Legionella and/or other bacteria. In the past there have been difficulties in developing rapid kits because of undesirable cross-reactions of specimens such as urine with antiserum. The use of monoclonal antibodies can eliminate these problems and provide highly specific and rapid tests for diagnosis. For example, a kit can be used in pathology laboratories for the rapid detection of gram-negative bacteria in urine, or on an out-patient basis.
  • conjugated or labelled monoclonal antibodies for antigens and/or species of Legionella and other gram-negative bacteria can be utilised in a kit to identify such antigens and organisms in blood samples taken from patients for the diagnosis of possible Legionella or other gram-negative sepsis.
  • the monoclonal test is an advance over existing procedures in that it is more accurate than existing tests; it gives "same day” results, provides convenience to the patient and improves therapy as a result of early, accurate diagnosis? and it reduces labour costs and laboratory time required for administration of the tests.
  • kit could be included as a component in a comprehensive line of compatible immunoassay reagents sold to reference laboratories to detect the species and serotypes of Legionella.
  • One preferred embodiment of the present invention is a diagnostic kit comprising at least one labelled monoclonal antibody against a particular Legionella antigen or species, as well as any appropriate stains, counterstains, or reagents. Further embodiments include kits containing at least one control sample of a Legionella antigen and/or a cross-reactive labelled monoclonal antibody which can detect the presence of any of the Legionella organisms in a particular sample. Specific antigens to be detected in this kit include the antigen of Legionella pneumophila (or a subspecies thereof) .
  • Monoclonal diagnostics which detect the presence of Legionella antigens can also be used in periodic testing of water sources, food supplies and food processing operations.
  • the present invention describes the use of the labelled monoclonal antibodies to determine the presence of a standard antigen
  • the invention can have many applications in diagnosing the presence of antigens by determining whether specimens such as urine, blood, stool, water and milk contain the particular Legionella antigen. More particularly, products of the invention could be utilised as a public health and safety diagnostic aid, whereby specimens such as water or food could be tested for possible contamina ⁇ tion.
  • the monoclonal antibody of the present invention was prepared generally according to the method of Kohler and Milstein, Eur. J. Immunol. 6_ (1975) 292.
  • DMEM Dulbeccos Modified Eagles Medium
  • FCS Foetal Calf Serum
  • % T refers to vaccine concentrations measured in a 1 cm light path
  • Legionella pneumophila serogroup 1 antigen Porton Down strain 1585 was grown on buffered charcoal yeast extract agar for 48 hours. It was then scraped off into formol-saline, and treated with Triton x 100/EDTA.
  • mice were injected with the prepared antigen. They were given an im injection + CFA, then an ip injection + PBS 4 weeks later. The -mice were rested for 10 weeks before being given a further injection (iv + PBS) . The mice were bled approximately six days after the last injection and the serum tested for antibodies by assay. The conventional assay used for this serum titer testing wa-s the enzyme-linked immunosorbent assay system. When the mice showed antibody production after this regimen, generally a positive titer of at least 10,000, a mouse was selected as a fusion donor and given a booster injection (0.02 ml of 80% T vaccine) intravenously, three days prior to splenectomy. C.
  • the selected donor mouse was killed and surface sterilised by immersion in 70% ethyl alcohol.
  • the spleen was then removed and immersed in approximately 2.5 ml of DMEM to which had been added 3% FCS.
  • the spleen was then gently homogenised in a LUX homogenising tube until all cells had been released from the membrane, and the cells were washed in 5 ml 3% FCS-DMEM.
  • the cellular debris was then allowed to settle and the spleen cell suspension placed in a 10 ml centrifuge tube. The debris was then rewashed in 5 ml 3% FCS-DMEM. 50 ml of suspension were then made in 3% FCS-DMEM.
  • myeloma cell line NSO (uncloned) , obtained from the MRC Laboratory of Molecular Biology in Cambridge, England, myeloma cells were obtained in the log growth phase, and rapidly dividing. Each cell line was washed using a tissue culture medium DMEM containing 3% FCS.
  • the spleen cells were then spun down at the same time that a relevant volume of myeloma cells was spun down (room temperature for 7 minutes at 600 g) , and each resultant pellet was then separately resuspended in 10 ml 3% FCS-DMEM.
  • 0.1 ml of the suspension was diluted to 1 ml and a haemacytometer with phase microscope was used.
  • 0.1 ml of the suspension was diluted to 1 ml with Methyl Violet-citric acid solution, and a haemacytometer and light microscope were used to count the stained nuclei of the cells.
  • each well contains 1.0 ml of the standard HAT medium (hypoxa thine, aminopterin and thymidine) and a feeder 4 layer of Balb/c macrophages at a concentration of 5x10 macrophages/well.
  • HAT medium hyperxa thine, aminopterin and thymidine
  • the wells were kept undisturbed and cultured at 37°C in 9% CO, air at approximately 100% humidity.
  • the wells were analysed for growth utilising the conventional inverted microscope procedure, after about 5 to 10 days.
  • the monoclonal antibodies from the clones were screened by the standard techniques for binding to the Legionella antigen prepared as in the immunisation, and for specificity in a test battery of Legionella species and related genera bearing different antigens.
  • the SP-Sephadex was allowed to settle and the supernatant decanted.
  • the SP-Sephadex was packed in a column, washed with 60 ml of 0.1M acetate buffer, pH 5.0, and eluted with 60 ml of the same buffer plus 1M sodium chloride.
  • the eluate was stirred at +4 C, and an equal volume of saturated ammonium sulphate added slowly.
  • the suspension was stirred for a further 30 minutes, and then the precipitate was harvested by centrifugation at 10,000 g for 10 minutes.
  • the precipitate was dissolved in a minimum volume of cold phosphate/EDTA buffer (20 mM sodium phosphate, 10 mM EDTA pH 7.5 + 0.02% sodium azide) .
  • the dialysed, redissolved precipitate was centrifuged at 30,000 g for 10 minutes and applied to a 10 ml column of DEAE-cellulose, previously equilibrated in phosphate/EDTA buffer.
  • the monoclonal antibody was eluted with phosphate/EDTA buffer.
  • H. Enzyme-Monoclonal Linkage The monoclonal antibody specific against the Legionella antigen, prepared and screened as described above, was then bound to an appropriate enzyme (in this case, a highly purified alkaline phosphatase) .
  • 24 mg alkaline phosphatase (Sigma Type VII-T) were dialysed against 2 x 500 ml of 0.25 M sodium phosphate buffer, pH 6.0, at +4 C.
  • Dialysed antibody was added to 4 mg of benzoquinone-activated alkaline phosphatase and immediately followed by sufficient IM sodium bicarbonate to give a final concentration of 0.1M.
  • the conjugation mixture was left in the dark at +4 C for 48 hours.
  • Sufficient IM lysine was then added to give a final concentration of 0.1M.
  • the conjugate was dialysed against 2 x 1000 ml PBS + 0.02% sodium azide at +4 C. An equal volume of glycerol was added.
  • the conjugate was sterile-filtered through a 0.22 ⁇ m membrane filter into a sterile amber vial, and stored at +4 C.
  • the enzyme immunoassay method was used for testing. This assay method comprises coating the wells of a standard polyvinyl chloride microtiter tray with the antigen, followed by addition of monoclonal antibody enzyme conjugate, and finally addition of the enzyme substrate, para-nitrophenol phosphate.
  • the monoclonal antibody was found to be specific for the antigen of Legionella.
  • the monoclonal antibody was also tested and shown to be of the immunoglobulin Class.
  • the particular epitopic site to which the antibody attaches to the antigen can also be determined.
  • the same enzyme immunoassay method can also be used to determine whether diagnostic specimens such as urine, blood, stool, water or milk contain the antigen.
  • the antibody can first be bound to the plate.
  • Example 2 The same procedure as in Example 1 may be utilised to prepare a monoclonal antibody to L. pneumophilia serogroup 1 obtained as organisms grown in continuous culture from Porton Down, England, with the exceptions that the antigen was prepared as an outer membrane preparation from the continuous culture, the immunised animals were C57/B10 mice, there was a 3 weeks interval g between the im and ip injections, and 1 x 10 spleen cells were used.
  • the first an example of a serogroup 1 strain, is specific to L. pneumophilia 1585.
  • Example 1 or Example 2 may be utilised in preparing a monoclonal antibody broadly cross-reactive with an antigen of many or all species of the genus Legionella, but using another Legionella obtained from the National Collection of Type Cultures.
  • Tests using the present invention are superior to the existing tests based on the following advantages: (i) greater accuracy? (ii) same day results, within an hour or two; (iii) reduction in amount of skilled labour required to administer laboratory procedures, resulting in reduced labour costs ? (iv) reduction in laboratory time and space used in connection with tests, resulting in reduced overhead expense? and (v) improved therapy based upon early, precise diagnosis.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

Anticorps monoclonaux au gène Legionella, anticorps marqués, compositions et kits contenant lesdits anticorps, et leur utilisation dans la diagnose d'antigènes et pour des traitements.
PCT/GB1987/000279 1986-04-25 1987-04-27 Anticorps monoclonaux et leur utilisation WO1987006469A1 (fr)

Applications Claiming Priority (2)

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GB8610203 1986-04-25
GB868610203A GB8610203D0 (en) 1986-04-25 1986-04-25 Monoclonal antibodies

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9017311U1 (de) * 1990-12-21 1991-05-29 Müller, Hans E., Prof. Dr.med. Dr.rer.nat., 3300 Braunschweig Testantigene zur intrakutanen Anwendung in der medizinischen und veterinärmedizinischen Diagnostik
FR2872289A1 (fr) * 2004-06-29 2005-12-30 Abag Sa Utilisation de la proteine g5 dans le diagnostic in vitro d'infection a legionella pneumophila
WO2006010805A3 (fr) * 2004-06-29 2006-06-22 Abag Sa Nouveaux polypeptides pour la mise en evidence in vitro et la prevention des infections a legionella pneumophila

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0119893A1 (fr) * 1983-02-21 1984-09-26 Centre National De La Recherche Scientifique (Cnrs) Anticorps monoclonaux anti-Légionella, procédé d'obtention et application au dosage de Légionella pneumophila
EP0165658A2 (fr) * 1984-06-20 1985-12-27 Board Of Regents, The University Of Texas System Procédés et compositions pour la détection de la maladie du légionnaire

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0119893A1 (fr) * 1983-02-21 1984-09-26 Centre National De La Recherche Scientifique (Cnrs) Anticorps monoclonaux anti-Légionella, procédé d'obtention et application au dosage de Légionella pneumophila
EP0165658A2 (fr) * 1984-06-20 1985-12-27 Board Of Regents, The University Of Texas System Procédés et compositions pour la détection de la maladie du légionnaire

Non-Patent Citations (13)

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Title
Biogical Abstracts, Vol. 77, No. 8, 1984 (Phila., PA, US) K.K. SETHI et al.: "Establishment of Hybridoma Cell lines Secreting Anti-Legionella Pneumophila Serogroup 1 Monoclonal Antibodies with Immunodiagnostic Potential", see page 6640, Abstract No. 60426, & Zentralbl Bakteriol Mikrobiol Hyg 1 Abt Orig A 255(2/3): 294-298, 1983 *
Biogical Abstracts, Vol. 80, No. 3, 1985 (Phila., PA, US) T. MIYAZAKI et al.: "Production of Monoclonal Antibodies against Legionella Pneumophila Serogroup 1", see page AB445, Abstract No. 22290, & Microbiol Immunol 29(3): 275-284, 1985 *
Biological Abstracts, Vol. 76, No. 8, 1983 (Phila., PA, US) K.K. SETHI et al. "Hybridoma-Derived Monoclonal Immunoglobulin M Antibodies to Legionella Pneumophils Serogroup 1 with Diagnostic Potential", see page 6237, Abstract No. 57107, & J Clin Microbiol 17(6): 953-957, 1983 *
Biological Abstracts, Vol. 77, No. 6, 1984 (Phila., PA, US) J.G. GUILLET et al.: "Characterization, Serological Specificity and Diagnostic Possibilities of Monoclonal Antiebodies against Legionella Pneumophila", see page 4867, Abstract No. 44543, & J Clin Microbiol 18(4): 793-797, 1983 *
Biological Abstracts, Vol. 77, No. 7, 1984 (Phila., PA, US) J.R. JOLY et al.: "Serogrouping and Subtyping of Legionella Pneumophila with Monoclonal Antibodies", see page 5760, Abstract No. 52491, & J Clin Microbiol 18(5): 1040-1046, 1983 *
Biological Abstracts, Vol. 79, No. 1, 1985 (Phila., PA, US) W.F. BIBB et al.: "Detection of Soluble Legionella Pneumophila Antigens in Serum and Urine Specimens by Enzyme-Linked Immunosorbent Assay (Elisa) with Monoclonal and Poluclonal Antibodies" see page AB-55-, Abstract No. 5060, & J Clin Microbiol 20(3): 478-482, 1984 *
Biological Abstracts, Vol. 79, No. 6, 1985 (Phila., PA, US) J.R. JOLY et al. "Correlation of Subtypes of Legionella Pneumophila Defined by Monoclonal Antibodies with Epidemiological Classification of Cases and Environment Sources", see page AB-38, Abstract No. 46154 & J Infect Dis 150(5): 667-671, 1984 *
Biological Abstracts, Vol. 81, No. 11, 1986 (Phila., PA, US) F.C. TENOVER et al.: "Comparison of Cross-Staining Reactions by Pseudomonas Spp. and Fluorescein-Labeled Polyclonal and Monoclonal Antibodies Directed against Legionella Pneumophila", see page AB-600, Abstract No. 103162, & J Clin Microbiol 23(3): 647-649, 1986 *
Biological Abstracts, Vol. 81, No. 12, 1986 (Phila., PA, US) J.R. JOLY et al.: "Development of a Standardized Subgrouping Scheme for Legionella Pneumophila Serogroup 1 using Monoclonal Antibodies", see page AB-461, Abstract No. 111776, & J Clin Microbiol 23(4): 768-771, 1986 *
Biological Abstracts, Vol. 81, No. 6, 1986 (Phila., PA, US) I.D. WATKINS et al.:"Legionella Pneumophila Serogroup 1 Subgrouping by Monoclonal Antibodies: An Epidemiological Tool", see page AB957, Abstract No. 57454, & J Hyg 95(2): 211-216, 1985 *
CHEMICAL ABSTRACTS, Vol. 102, No. 3, 21 January 1985 (Columbus, Ohio, US) L.H. GOSTING et al.: "Identification of a Species-Specific Antigen in Legionella Pneumophila by a Monoclonal Antibody", see page 516, Abstract No. 22512y, & J. Clin. Microbiol. 1984, 20(6), 1031-5 *
CHEMICAL ABSTRACTS, Vol. 102, No. 9, 4 March 1985 (Columbus, Ohio, US) S.L. BROWN et al.: "Use of Monoclonal Antiebodies in an Epidemiological Marker System: a Retrospective Study of lung Specimens from the 1976 outbreak of Legionnaires Disease in Philadelphia by indirect Fluorescent-Antibody and Enzyme-Linked Immunosorbent Assay Methodes", see pages 260-261, Abstract No. 74966r, & J. Clin. Microbiol. 1985, 21(1), 15-9 *
Monoclonal Antibodies against Bacteria, Vol. 1, 1985, Edited by A.J.L. Macario and E. Conway de Macario, Academic Press (New York, US) K.K. Sethi: "Monoclonal Antibodies against Legionella Pneumophila Serogroup 1 Antiges: Characterization and their Potential Applications", see pages 121-133 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9017311U1 (de) * 1990-12-21 1991-05-29 Müller, Hans E., Prof. Dr.med. Dr.rer.nat., 3300 Braunschweig Testantigene zur intrakutanen Anwendung in der medizinischen und veterinärmedizinischen Diagnostik
FR2872289A1 (fr) * 2004-06-29 2005-12-30 Abag Sa Utilisation de la proteine g5 dans le diagnostic in vitro d'infection a legionella pneumophila
WO2006010805A3 (fr) * 2004-06-29 2006-06-22 Abag Sa Nouveaux polypeptides pour la mise en evidence in vitro et la prevention des infections a legionella pneumophila

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