WO1993017044A1 - Immunoglobuline humaine dirigee pour la prevention et le traitement de staphylococcies - Google Patents

Immunoglobuline humaine dirigee pour la prevention et le traitement de staphylococcies Download PDF

Info

Publication number
WO1993017044A1
WO1993017044A1 PCT/US1992/009830 US9209830W WO9317044A1 WO 1993017044 A1 WO1993017044 A1 WO 1993017044A1 US 9209830 W US9209830 W US 9209830W WO 9317044 A1 WO9317044 A1 WO 9317044A1
Authority
WO
WIPO (PCT)
Prior art keywords
epidermidis
immune globulin
human immune
directed
screened
Prior art date
Application number
PCT/US1992/009830
Other languages
English (en)
Inventor
Gerald W. Fischer
Original Assignee
U.S. Government, As Represented By The Secretary Of The Army
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 U.S. Government, As Represented By The Secretary Of The Army filed Critical U.S. Government, As Represented By The Secretary Of The Army
Priority to EP93901435A priority Critical patent/EP0628056A4/fr
Priority to AU32718/93A priority patent/AU673508B2/en
Priority to JP5514800A priority patent/JPH08504167A/ja
Publication of WO1993017044A1 publication Critical patent/WO1993017044A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/18—Testing for antimicrobial activity of a material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • 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
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/77—Internalization into the cell
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
    • G01N2333/305—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F)
    • G01N2333/31—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Micrococcaceae (F) from Staphylococcus (G)

Definitions

  • This invention relates to Directed Human Immune Globulin for the prevention and treatment of staphylococcal infections. III. BACKGROUND OF THE INVENTION
  • staphylococci have become important causes of infection in hospitalized patients. Because of their high prevalence on the skin, staphylococci are ideally situated to cause serious infections in debilitated or immunosuppressed patients.
  • the staphylococcal species most frequently pathogenic in humans are Staphylococcus aureus (SA) and
  • SE Staphylococcus epidermidis
  • SE has emerged as a common cause of neonatal nosocomial sepsis in premature infants.
  • SE infections frequently occur in immature babies that have received parenteral nutrition.
  • Premature babies have impaired immunity with deficiencies in antibodies, complement and neutrophil function.
  • Lipid infusion is now a standard ingredient of parenteral nutrition therapy in many nurseries and may further impair immunity to bacterial infection as disclosed by Fischer and colleagues (Lancet, 1980; 2:819-20).
  • Recent studies have associated coagulase negative staphylococcal bacteria in neonates with lipid emulsion infiision (Freeman and colleagues, N. Engl. J. Med, 1990).
  • the opsonic assays that are currently used are slow and cumbersome for screening blood, plasma or immune globulin for antibodies to SE. It would be important to have a rapid antigen binding assay to screen for SE antibody, if that assay further correlated with opsonic activity in vitro and protection in vivo.
  • Yoshida and collegues (J Microbiol, 1976) reported on a virulent strain of SE that infected mature mice with 90 - 100% of mice dying within 24 - 48 hours. This model is very different from that seen in patients and may represent an unusual type of SE infection. When they analyzed 80 fresh isolates of SE from humans, they were not able to kill mice. Non-human antibody to a new SE surface polysaccharide protected the mice from the virulent SE strain. A later report by Yoshida and colleagues (J Med
  • mice In the animal model described by Yoshida, Ichiman and colleagues mature, non-immunosuppressed mice were used and death was considered to be related to toxins not sepsis (Yoshida and colleagues, J.
  • Antibody provides protection in humans against certain .
  • encapsulated bacteria such as Hemophilus influenzae and Streptococcus pneumoniae.
  • Individuals such as young infants who are deficient in antibody are susceptible to infections with these bacteria and bacteremia and sepsis are common. When antibody to these bacteria is present it provides protection by promoting clearance of the bacteria from the blood. Immunoglobulin with antibody to H. influenzae and S. pneumoniae protects infants from sepsis with these bacteria.
  • the article by Espersen and colleagues, (Arch Intern Med, 1987) discloses the use of an antigen binding RIA assay to analyze IgG antibody to SE in patients with uncomplicated bacteremia and those with bacteremia and endocarditis.
  • This assay used an ultrasonic extract of SE to identify SE specific IgG (the surface antigen in this study differs from the antigen used by Yoshida and colleagues which was obtained by a different method; gentle sonic oscillation). None of the patients with uncomplicated bactermia had IgG antibodies to SE. These data would suggest that IgG is unnecessary for effective eradication of SE from the blood. In addition, 89% of bacteremic patients with endocarditis developed high levels of IgG to SE. In these patients, IgG was not protective since high levels of IgG antibody (which may have developed late) were associated with serious bacteremia and endocarditis.
  • SE is an important pathogen in certain high risk individuals, such as patients with foreign body implants, premature neonates and immunosuppressed patients. Accordingly there is a need for a human immune globulin that would prevent or treat SE infections such as, sepsis or endocarditis and promote clearance of SE from the blood of such high risk people. IV. SUMMARY OF THE INVENTION
  • Directed Human Immune Globulin is different from standard human immune globulin preparations in that it has high levels of human anti-staphylococcal antibodies that react with surface antigens of S. epidermidis and enhance phagocytosis and killing of S. epidermidis in vitro, (opsonophagocytic bactericidal activity greater than 80%).
  • Directed Human Immune Globulin for S . epidermidis enhances immunity in vivo and prevents lethal infection as well as enhancing clearance of S. epidermidis from the blood in conditions of immaturity and impaired immunity. This is surprising since
  • Immune Globulin when given intravenously immediately provides specific antibodies to promote phagocytosis and killing of S. epidermidis by
  • a further advantages of the present invention is that by providing opsonic antibody to immature or immunosuppressed patients infected with SE, antibiotic therapy may be enhanced by improved S. epidermidis clearance from the blood or site of infection. Another advantage is that since Directed Human Immune Globulin given intravenously or intramuscularly can raise the level of antibodies in the blood of patients, Directed Human Immune Globolin could prevent S. epidermidis from causing bacteremia and local infections.
  • the method of producing the Directed Human Immune Globulin for S. epidermidis involves:
  • a) screening plasma (pools of immunoglobulin or plasma; immunoglobulin or immunoglobulin preparations) for antibodies to S. epidermidis using an in vitro antigen-binding assay: (ELISA), followed by confirmation of functional activity using an in vitro opsonophagocytic bactericidal assay (bactericidal activity greater than 80%).
  • ELISA in vitro antigen-binding assay
  • Directed Human Immune Globulin for SE could be used to prevent lethal SE infections in high risk patients such as neonates and adults in intensive care units or patients with in-dwelling foreign bodies such as venous and arterial catheters or ventricular shunts. Directed Human Immune Globulin could also be used in addition to antibiotics as adjunctive therapy to enhance bacterial clearance in patients treated for SE infections.
  • Standard Human Immunoglobulin and Directed Human Immune Globulin for JJL epidermidis as used in this application are defined as follows: Standard Human Immunoglobulin - immune human globulin that was prepared by pooling immunoglobulin from many donors, without selecting donors or screening the immunoglobulin to ensure antibody acitivity for S. Epidermidis.
  • Figure 1 shows that when several pools of human standard intravenous immunglobulin were analyzed, there was a marked difference in the antibody activity to S. epidermidis as measured by an antigen binding assay (ELISA, highest O.O. reading at 1 1/2 hrs using 1:100 Dil). These were large pools of IgG, purified by several companies using various techniques. Of three pools with the highest titers, two were from Cutter Laboratories, Berkeley
  • Figure 2 shows that using an in vitro functional (opsonic) assay that measures the ability of immunoglobulin to promote phagocytosis and killing of S. epidermidis by neutrophils in the presence of complement, that opsonic activity is also variable in various lots and preparations of standard human immunoglobulin.
  • the figure also shows that the immunoglobulins identified by ELISA as having high levels of antibody to S. epidermidis also had high levels of functional antibody in vitro. This is critical since this study shows that IgG that binds to TCA extracted S. epidermidis antigen will promote phagocytosis and killing of S. epidermidis. Therefore, using in vitro screening assays, one could select a Directed Human Immune Globulin for S.
  • epidermidis that would have reliable levels of antibody to prevent or treat S. epidermidis infections.
  • FIG. 3 shows that Directed Immune Globulin protects animals from developing prolonged S. epidermidis bacteremia while standard immune globulin did not.
  • Animals treated with Directed Immune Globulin had lower peak bacteremia levels (9.2 ⁇ 10 2 vs. 6.5 ⁇ 10 3 ) and cleared the bacteremia more efficiently (at 72 hours, 5 bact. per ml vs. 380 bact. per ml; geometric mean level).
  • 72 hours after infection 18/24 (75%) animals given Directed Immune Globulin had cleared their bacteremia and 100% survived, while only 4/20 (20%) animals given standard immune globulin died and only 1/16 (6%) cleared their bacteremia during that 72 hour period.
  • Directed Immune Globulin enhanced S. epidermidis
  • Staphylococcal Strains Although any S. epidermidis strains could be used, in these experiments we used two strains from the American Type Culture Collection, Rockville, MD (ATCC #31432 and ATCC #35984). A clinical isolate (Hay) from the blood of a child with S. epidermidis sepsis was also used and is also on deposit at the American Type Culture Collection.
  • Immunoglobulin Standard Intravenous Immunoglobulin was used in these experiments to represent large immunoglobulin pools.
  • Trichloroacetic Acid (TCA) Antigen Extraction Staphylococcus epidermidis strains ATCC #35984, ATCC #31432 and Hay were grown to log phase at 37°C in 1000 ml of Tryptic Soy Broth (Difco). The bacteria were then centrifuged at 2500 RPM for 10 minutes and the supernatant was aspirated and discarded.
  • the bacterial button was resuspended in 200 ml of 2% trichloroacetic acid (TCA) and stirred overnight at 4°C. The mixture was then centrifuged at 2500 RPM for 10 minutes and the supernatant aspirated. To the supernatant, 4 volumes of absolute ethanol were added and refrigerated overnight at 4°C. After centrifiigation at 2500 RPM for 10 minutes, the supernatant was removed and discarded. Then, five milliliters of normal saline was added to the antigen precipitate, it was cultured to ensure sterility and then lyophilized for storage.
  • TCA 2% trichloroacetic acid
  • Immunoabsorbent Assay S. epidermidis Antigen was dissolved in carbonate buffer at a concentration of 25 micrograms/ml. To each well of A 96-well flat-bottomed microtiter plate (NUNC, Roskilide, Denmark) 100 microliters were added and stored at 4°C until used. Immunoglobulin was diluted to 1 % and 2-fold dilutions prepared in phosphate-buffered saline-Tween . To each weir was added 100 microliters of the serial dilutions and the plates were incubated for 1 hour at 4°C. The plates were washed four times with H 2 O-Tween .
  • neutrophil mediated bactericidal assay was used. Neutrophils were isolated from adult venous blood by dextran
  • a suckling rat model was used to determine the in vivo activity of antibody to S. epidermidis.
  • Wistar rats (2 days old) were given 0.2 ml of 20% Intralipid (Cutter, Berkeley California,) intraperitoneally at 0800 and 1400.
  • 0.2 ml of 20% intralipid at 0800 and 1400 and 0.2 ml of 5% immunoglobulin or serum was given IP.
  • 0.05ml approximately 0.05ml (approx. 5 ⁇ 10 7 ) mid log phase S. epidermidis were injected subcutaneously just cephalad to the tail.
  • Suckling rats less than 24 hours old also develop lethal S.
  • epidermidis sepsis when infected with 10 7 -10 8 S. epidermidis subcutaneously.
  • 0.01 ml of blood was obtained from the tails of the suckling rats, 24, 48, and 72 hours after infection.
  • The. blood was collected under sterile conditions in micropipettes and serially diluted in Tryptic Soy Broth (Difco). Bacteria were subcultured onto plates to ensure S. epidermidis bacteremia and all animals were followed five days to determine survival.
  • epidermidis based on in vitro assays that measured antibody binding to TCA S. epidermidis antigens and opsonic antibody activity determined by in vitro testing. Serum from a single donor also had good opsonic activity for S. epidermidis (> 80% opsonophagocytic bactericidal activity). While serum and plasma from several individuals have been studied only this donor had high opsonic activity. Therefore donor screening could detect individual blood or plasma donors that could contribute immunoglobulin that could be pooled as an alternate method to produce a Directed Human Immune Globulin for S. epidermidis. In addition blood or plasma units could be screened for pooling as well. Animal Protection Studies
  • Table 1 shows the effect of Directed Human Immunoglobulin for S. epidermidis (40R09) (which was selected by ELISA and opsonic assay screening) compared to standard human immunoglobulin (that had moderate activity for S. epidermidis) and saline control. Table 1 shows that untreated control animals had about a 50% mortality while animals given Directed Immune Globulin for S. epidermidis were fully protected (NO mortality).
  • Table 2 demonstrates that Directed Immune Globulin produced in rabbits by immunization (S. epidermidis vaccine) produced survival similar to Directed Human Immune Globulin produced by screening immunoglobulin for antibody to S. epidermidis. Immunization of individuals with S.
  • Table 3 shows that intralipid causes a dose related increased mortality in suckling rats infected with S. epidermidis. Control animals receiving Intralipid alone had 100% survival (43/43) while immature rats given 16 gm/kg of Intralipid had only 46% survival (6/13). The high dose of Intralipid appears to impair the immune system sufficiently to allow the normally avirulent S. epidermidis to overwhelm the baby animals.
  • Table 4 shows that normal 3 day old suckling rats not given Intralipid, but infected with S. epidermidis develop bacteremia.
  • Table 1 shows the Directed Human Immune Globulin for S. epidermidis (selected by screening standard immunoglobulin for opsonic or antigen binding activity for S. epidermidis. provides complete protection from lethal infection in the setting of impaired immunity with. Intralipid while standard immune globulin (with moderate antibody levels) had only partial protection (1 out of 5 aminals died compared to about 50% with saline).
  • Directed Human Immune Globulin 8016A >90% opsonic activity, versus standard human immune globulin, 8007 A ⁇ 50% opsonic activity showed that the Directed Human Immune globulin also provided enhanced survival (8016A-64/95 (67%) vs. 8007A-39/90 (43%)) over standard human immune globulin. Even more striking was the fact that the Directed Human Immune Globulin decreased the peak level of S. epidermidis
  • epidermidis enhanced bacterial clearance from the blood and could be an effective prophylactic or therapeutic modality even in the immature host with impaired immunity.
  • Many of the animals treated with standard human immune globulin remained bacteremic 72 hours after infection while only 1/20 animals was still bacteremic at 72 hours after receiving the Directed Human Immune Globulin.
  • the mean bacteremia level at 72 hours was markedly different (bacteremia with Directed Human Immune Globulin 0.5 ⁇ 10 1 vs. bacteremia with standard human immune globulin 3.8 ⁇ 10 2 ).
  • rabbit Directed Immune Globulin for S. epidermidis was produced by immunizing rabbits with S. epidermidis vaccine.
  • the vaccine induced Directed Immune Globulin was compared with Directed Human Immune Globulin produced by screening immunoglobulin for antibody to S. epidermidis (Table 2).
  • Vaccine induced Directed Immune Globulin had similar protective activity to Directed Human Immune Globulin produced by screening (9/11 vs. 12/13 survived) and each was better than controls (11/19 survived).
  • epidermidis are not pathogenic in normal people. However, in babies with an immature immune system or impaired immunity as is seen with intralipid, S. epidermidis may cause sepsis and death. It is critical therefore, that any animal model to test antibody effectiveness should include these factors. To our knowledge this is the first time that antibody to Staphylococcus epidermis has been shown to provide protection and enhance bacterial clearance in an immature and/or immunosuppressed host. Intralipid given in dosage up to 16 gm/kg did not cause death in any baby animals (controls, table 3). In the absence of
  • Intralipid the 3 day old animals will become bacteremic with S. epidermidis after infection, but will clear the infection over 72 hours and survive (Table 4). However, Intralipid did impair immunity in a dose related fashion and when the 3 day old animals were infected with S. epidermidis lethal sepsis occurred in up to 67% of the animals. Baby rats in the first day of life also do not clear bacteriemia well (due to immature immunity) and develop lethal sepsis. In these models baby rats were unable to clear the S. epidermidis bacteremia and developed lethal sepsis. Directed Human Immune Globulin was able to enhance survival and promote bacterial clearance while standard human immune globulin did not enhance clearance (Fig 3).
  • Standard model starts IL on day 2 of life with infection after last IL dose on day 3 if full 4 doses given.
  • *IL started on day I of life with infection after the 4th dose on day 2.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Toxicology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention se rapporte à l'immunoglobuline humaine dirigée et à des compositions contenant ladite globuline pour la prévention et le traitement de staphylococcies telle que la Staphilococeis epidermidis.
PCT/US1992/009830 1992-02-25 1992-11-09 Immunoglobuline humaine dirigee pour la prevention et le traitement de staphylococcies WO1993017044A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP93901435A EP0628056A4 (fr) 1992-02-25 1992-11-09 Immunoglobuline humaine dirigee pour la prevention et le traitement de staphylococcies.
AU32718/93A AU673508B2 (en) 1992-02-25 1992-11-09 Directed human immune globulin for the prevention and treatment of staphylococcal infections
JP5514800A JPH08504167A (ja) 1992-02-25 1992-11-09 スタフィロコーカス感染の予防及び処理のための指図されたヒト免疫グロブリン

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US80431792A 1992-02-25 1992-02-25
US804,317 1992-02-25

Publications (1)

Publication Number Publication Date
WO1993017044A1 true WO1993017044A1 (fr) 1993-09-02

Family

ID=25188685

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1992/009830 WO1993017044A1 (fr) 1992-02-25 1992-11-09 Immunoglobuline humaine dirigee pour la prevention et le traitement de staphylococcies

Country Status (5)

Country Link
EP (1) EP0628056A4 (fr)
JP (1) JPH08504167A (fr)
AU (1) AU673508B2 (fr)
CA (1) CA2117480A1 (fr)
WO (1) WO1993017044A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0694309A2 (fr) * 1994-07-29 1996-01-31 The Kitasato Institute Compositions vaccinales contenant des antigènes et des anticorps pour la prévention et l'inhibition d'infections induites par les staphylocoques
EP1027896A1 (fr) * 1992-03-19 2000-08-16 Henry M. Jackson Foundation For The Advancement Of Military Medicine Anticorps opsoniques fortement réactifs,réagissant aux antigènes communs des staphylocoques
US6660842B1 (en) 1994-04-28 2003-12-09 Tripep Ab Ligand/receptor specificity exchangers that redirect antibodies to receptors on a pathogen
US6692739B1 (en) 1998-08-31 2004-02-17 Inhibitex, Inc. Staphylococcal immunotherapeutics via donor selection and donor stimulation
US6933366B2 (en) 1996-12-27 2005-08-23 Tripep Ab Specificity exchangers that redirect antibodies to bacterial adhesion receptors
US6939543B2 (en) 1997-06-16 2005-09-06 Henry M. Jackson Foundation For The Advancement Of Military Medicine Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria
WO2007060546A2 (fr) * 2005-05-31 2007-05-31 Bengt Guss Caracterisation de proteines de staphylococcus epidermidis portant le motif lpxtg
US7250494B2 (en) 1998-06-15 2007-07-31 Biosynexus Incorporated Opsonic monoclonal and chimeric antibodies specific for lipoteichoic acid of Gram positive bacteria
US7318926B2 (en) 2003-02-06 2008-01-15 Tripep Ab Glycosylated specificity exchangers
US7335359B2 (en) 2003-02-06 2008-02-26 Tripep Ab Glycosylated specificity exchangers
EA016268B1 (ru) * 2009-05-12 2012-03-30 Государственное Учреждение ''Республиканский Научно-Практический Центр Трансфузиологии И Медицинских Биотехнологий'' Способ получения антистафилококковой плазмы крови
WO2013156976A1 (fr) * 2012-04-20 2013-10-24 Universite Pierre Et Marie Curie (Paris 6) Prevention et traitement des infections non virales chez des individus traites par des immunosuppresseurs

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4027010A (en) * 1975-04-10 1977-05-31 Anatoly Efimovich Kiselev Antistaphylococcous human immunoglobulin and method of preparing same
US4197290A (en) * 1977-09-30 1980-04-08 Kosaku Yoshida Vaccine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4027010A (en) * 1975-04-10 1977-05-31 Anatoly Efimovich Kiselev Antistaphylococcous human immunoglobulin and method of preparing same
US4197290A (en) * 1977-09-30 1980-04-08 Kosaku Yoshida Vaccine

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Infection and Immunity, Volume 42, No. 3, issued December 1983, T.E. WEST et al.: "Detection of Anti-Teichoic Acid Immunoglobulin G Antibodies in Experimental Staphylococcus Epidermidis Endocarditis", pages 1020-1026, especially page 1020. *
J. Clin. Pathol., Volume 39, issued 1986, L. CLARK et al.: "Opsonic Activity of Intravenous Immunoglobulin Preparations Against Staphylococcus Epidermidis", pages 856-860, especially page 856. *
Journal of Applied Bacteriology, Volume 63, issued 1987, Y. ICHIMAN et al.: "Protective Antibodies in Human Sera Against Encapsulated Strains of Staphylococcus Epidermidis", pages 165-169, especially page 165. *
Journal of Clinical Microbiology, Volume 23, No. 2, issued February 1986, F. ESPERSEN et al.: "Enzyme-Linked Immunosorbent Assay for Detection of Staphylococcus Epidermidis Antibody in Experimental S. Epidermidis Endocarditis", pages 339-342, especially page 339. *
See also references of EP0628056A4 *
The Lancet, issued 18 October 1980, G.W. FISCHER et al.: "Diminished Bacterial Defences with Intralipid", pages 819-820, especially page 819. *
The New England Journal of Medicine, Volume 323, No. 5, issued 02 August 1990, J.O. KLEIN: "From Harmless Commensal to Invasive Pathogen Coagulase-Negative Staphylococci", pages 339-340. *

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1027896A1 (fr) * 1992-03-19 2000-08-16 Henry M. Jackson Foundation For The Advancement Of Military Medicine Anticorps opsoniques fortement réactifs,réagissant aux antigènes communs des staphylocoques
EP0635132B1 (fr) * 1992-03-19 2000-11-08 Henry M. Jackson Foundation For The Advancement Of Military Medicine Anticorps opsoniques fortement reactifs, reagissant aux antigenes communs des staphylocoques
US7019111B2 (en) 1994-04-28 2006-03-28 Tripep Ab Glycosylated ligand/receptor specificity exchangers specific for bacterial adhesion receptors
US6660842B1 (en) 1994-04-28 2003-12-09 Tripep Ab Ligand/receptor specificity exchangers that redirect antibodies to receptors on a pathogen
EP0694309A3 (fr) * 1994-07-29 1998-04-22 The Kitasato Institute Compositions vaccinales contenant des antigènes et des anticorps pour la prévention et l'inhibition d'infections induites par les staphylocoques
US6391315B1 (en) 1994-07-29 2002-05-21 Takahashi Hashimoto Vaccine for inhibiting and preventing induced staphylococcus infection, isolated antigens used therein, and isolated antibodies induced thereby
EP0694309A2 (fr) * 1994-07-29 1996-01-31 The Kitasato Institute Compositions vaccinales contenant des antigènes et des anticorps pour la prévention et l'inhibition d'infections induites par les staphylocoques
US6933366B2 (en) 1996-12-27 2005-08-23 Tripep Ab Specificity exchangers that redirect antibodies to bacterial adhesion receptors
US6939543B2 (en) 1997-06-16 2005-09-06 Henry M. Jackson Foundation For The Advancement Of Military Medicine Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria
US7511122B2 (en) 1997-06-16 2009-03-31 Henry M. Jackson Foundation For The Advancement Of Military Medicine Humanized and chimeric antibodies specific for lipoteichoic acid of GRAM positive bacteria
US8372958B2 (en) 1997-06-16 2013-02-12 Biosynexus Incorporated; Opsonic and protective monoclonal and chimeric antibodies specific for lipoteichoic acid of gram posiive bacteria
US7884198B2 (en) 1997-06-16 2011-02-08 The Henry M. Jackon Foundation for the Advancement of Military Medicine Polynucleotides encoding humanized and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria
US7250494B2 (en) 1998-06-15 2007-07-31 Biosynexus Incorporated Opsonic monoclonal and chimeric antibodies specific for lipoteichoic acid of Gram positive bacteria
US7777017B2 (en) 1998-06-15 2010-08-17 Biosynexus Incorporated Nucleic acids encoding opsonic monoclonal and chimeric antibodies specific for lipoteichoic acid of gram positive bacteria
US7045131B2 (en) 1998-08-31 2006-05-16 Inhibitex, Inc. Staphylococcal immunotherapeutics via donor selection and donor stimulation
US6692739B1 (en) 1998-08-31 2004-02-17 Inhibitex, Inc. Staphylococcal immunotherapeutics via donor selection and donor stimulation
US7318926B2 (en) 2003-02-06 2008-01-15 Tripep Ab Glycosylated specificity exchangers
US7335359B2 (en) 2003-02-06 2008-02-26 Tripep Ab Glycosylated specificity exchangers
US7534435B2 (en) 2003-02-06 2009-05-19 Tripep Ab Glycosylated specificity exchangers
US7332166B2 (en) 2003-02-06 2008-02-19 Tripep Ab Glycosylated specificity exchangers
US8303956B2 (en) 2003-02-06 2012-11-06 Chrontech Pharma Ab Glycosylated specificity exchangers
US8658179B2 (en) 2003-02-06 2014-02-25 Chrontech Pharma Ab Glycosylated specificity exchangers
US9079962B2 (en) 2003-02-06 2015-07-14 Tripep Ab Glycosylated specificity exchangers
WO2007060546A3 (fr) * 2005-05-31 2007-12-27 Bengt Guss Caracterisation de proteines de staphylococcus epidermidis portant le motif lpxtg
WO2007060546A2 (fr) * 2005-05-31 2007-05-31 Bengt Guss Caracterisation de proteines de staphylococcus epidermidis portant le motif lpxtg
EA016268B1 (ru) * 2009-05-12 2012-03-30 Государственное Учреждение ''Республиканский Научно-Практический Центр Трансфузиологии И Медицинских Биотехнологий'' Способ получения антистафилококковой плазмы крови
WO2013156976A1 (fr) * 2012-04-20 2013-10-24 Universite Pierre Et Marie Curie (Paris 6) Prevention et traitement des infections non virales chez des individus traites par des immunosuppresseurs
FR2989589A1 (fr) * 2012-04-20 2013-10-25 Univ Paris Curie Prevention et traitement des infections non virales chez des individus traites par des immunosuppresseurs

Also Published As

Publication number Publication date
JPH08504167A (ja) 1996-05-07
AU673508B2 (en) 1996-11-14
AU3271893A (en) 1993-09-13
CA2117480A1 (fr) 1993-09-02
EP0628056A4 (fr) 1997-03-05
EP0628056A1 (fr) 1994-12-14

Similar Documents

Publication Publication Date Title
US5955074A (en) Directed human immune globulin for the prevention and treatment of staphylococcal infections
US5571511A (en) Broadly reactive opsonic antibodies that react with common staphylococcal antigens
JP4656728B2 (ja) ブドウ球菌抗原及びワクチン
EP0648127B1 (fr) Antigenes de surface du type i associes au staphylococcus epidermidis
US20080139789A1 (en) Isolated Broadly Reactive Opsonic Immunoglobulin for Treating a Pathogenic Coagulase-Negative Staphylococcus Infection
AU673508B2 (en) Directed human immune globulin for the prevention and treatment of staphylococcal infections
CA2132421C (fr) Anticorps opsoniques largement reactifs qui reagissent avec les antigenes des staphylocoques communs
Greenberg et al. Protective efficacy of protein A-specific antibody against bacteremic infection due to Staphylococcus aureus in an infant rat model
Fischer et al. Opsonic antibodies to Staphylococcus epidermidis: in vitro and in vivo studies using human intravenous immune globulin
US7279162B1 (en) Isolated broadly reactive opsonic immunoglobulin for treating a pathogenic coagulase-negative staphylococcus infection
JPH0284197A (ja) ヒトモノクローナル抗体
Lang et al. Isolation and characterization of a human monoclonal antibody that recognizes epitopes shared by Pseudomonas aeruginosa immunotype 1, 3, 4, and 6 lipopolysaccharides
Zweerink et al. X-linked immunodeficient mice as a model for testing the protective efficacy of monoclonal antibodies against Pseudomonas aeruginosa
CA2200691C (fr) Anticorps a activite opsonique etendue reagissant avec les antigenes du staphylocoque
WO1996009321A9 (fr) Anticorps a activite opsonique etendue reagissant avec les antigenes du staphylocoque
Yoshida et al. Successive extraction of specific protective immunoglobulins from pooled human sera
Herzberg et al. Nonabsorbable rabbit anti-Salmonella typhimurium antibody as detected by the complement-mediated bactericidal reaction
Okada et al. Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutans in the pathogenesis of poststreptococcal glomerulonephritis
Rozalska et al. Role of antibodies against fibronectin-, collagen-binding proteins and alphatoxin in experimental Staphylococcus aureus peritonitis and septicaemia in neutropenic mice
Lee injluenzae (Hib) capsular

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO PL RO RU SD SE US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL SE BF BJ CF CG CI CM GA GN ML MR SN TD TG

EX32 Extension under rule 32 effected after completion of technical preparation for international publication

Free format text: KZ

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
LE32 Later election for international application filed prior to expiration of 19th month from priority date or according to rule 32.2 (b)
EX32 Extension under rule 32 effected after completion of technical preparation for international publication
LE32 Later election for international application filed prior to expiration of 19th month from priority date or according to rule 32.2 (b)
WWE Wipo information: entry into national phase

Ref document number: 2117480

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1993901435

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1993901435

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1993901435

Country of ref document: EP